Background. Arterial hypertension (AH) and heart diseases are the leading causes of morbidity, mortality and the number of visits to the doctor. Cardiac patients are characterized by the frequent polymorbidity. The cardiovascular continuum, which predicts the course of events from atherosclerosis to the final stages of cardiovascular diseases (CVD), includes the following pathogenetic links: oxidative stress, inflammation and endothelial dysfunction (ED). Objective. To describe the management of a cardiac patient with comorbidity and promising options for the ED correction. Materials and methods. Analysis of the literature on this issue. Results and discussion. The previous paradigm of CVD development involved damage to target organs due to hypertension. Instead, according to the current paradigm, CVD are the result of the vascular dysfunction. The recently proposed paradigm indicates that all CVD are based on ED. Nitric oxide (NO) is the main molecule necessary for the proper functioning of the endothelium. NO takes part in the relaxation of blood vessels and smooth muscles, regulates the synthesis and secretion of a number of hormones, controls platelet activity and the interaction of leukocytes with vascular walls, participates in antipathogenic reactions of the immune system. ED is known to be a predictor of complications and poorer survival in patients with coronary heart disease. Dysfunctional endothelium promotes vasoconstriction, oxidation, inflammation and thrombosis. To improve the condition of the endothelium, it is advisable to increase the NO content. The increase in NO content can be the result of angiotensin-converting enzyme inhibitors, calcium channel blockers, sartans, statins, estrogens, antioxidants, and aspirin intake, as well as exercise. L-arginine is the substrate for the NO formation in human body. Potential mechanisms of L-arginine effect in AH include improvement of endothelial function, increase of vascular NO synthesis, decrease of endothelin-1 and angiotensin II activity, modulation of renal hemodynamics and reduction of oxidative stress. L-arginine therapy (9 g per day for 4 weeks) reduced systolic blood pressure by 4 mm Hg and diastolic – by 2.6 mm Hg. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. The use of L-arginine is well studied in patients with chronic heart failure (HF) with preserved ejection fraction. In this category of patients, such treatment leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF. The ESPEN guidelines on parenteral nutrition state that the use of L-arginine has both NO-dependent and NO-independent effects. The latter include the synthesis of creatine, proline and polyamines; stimulation of insulin and growth hormone secretion. Administration of L-arginine in combination with L-carnitine helps to eliminate the advanced glycation end products and to increase the rate of glomerular filtration. Conclusions. 1. The cardiovascular continuum includes such elements as oxidative stress, inflammation and endothelial dysfunction. 2. NO is the main molecule necessary for the proper functioning of the endothelium. 3. L-arginine is the substrate for the NO formation in human body. L-arginine also helps to improve endothelial function, to reduce the activity of endothelin-1 and angiotensin II, to modulate renal hemodynamics and to reduce oxidative stress. 4. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. 5. In patients with chronic HF with preserved ejection fraction, treatment with L-arginine leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF.

Background. Intoxication syndrome (IS) is one of the most common syndromes in the medical practice, but its exact scientific outline has not yet been established. This is due to a variety of toxic factors, a large polymorphism of symptoms, and complex interactions between the processes of toxin production and detoxification. Objective. To describe the main features of IS and its treatment. Materials and methods. Analysis of literature sources on this issue. Results and discussion. The morphological basis of IS is the subcellular interaction between the toxin and the receptor. IS develops if the toxins’ entry or formation outweigh their elimination. Intoxications are divided into exogenous and endogenous. The diagnostic criteria for exogenous intoxications are the contact of the patient with the substance that caused the intoxication and the corresponding damage to the organs. Exogenous intoxications have a clear clinical picture, and the introduction of specific antidotes or antitoxins is the best treatment. In turn, endogenous IS is mediated by the accumulation of bacterial endotoxins, excess amounts of physiological metabolic products, biologically active substances and mediators. Natural ways of detoxification include metabolism, excretion and immune mechanisms. Infusion detoxification (IDT) with a significant load by crystalloids and multicomponent drugs is a mandatory treatment for both exogenous and endogenous IP. In most cases, the volume of infusion should be 25-35 ml/kg body weight. Requirements for the ideal drug for detoxification include hypervolemia, improving microcirculation and rheological properties of blood, correction of electrolyte disorders and disorders of acid-base balance, increase of diuresis and peristalsis. All these effects are typical for Reosorbilact (“Yuria-Pharm”). In general, the IDT program may include classical and balanced crystalloids (800-1500 ml), Reosorbilact (600-800 ml), specialized solutions (100-200 ml), and symptomatic drugs. The optimal duration of treatment with Reosorbilact is 7 days. Conclusions. 1. Exact scientific characteristics of IS are still missing. 2. IDT is the mandatory method of treatment of exogenous and endogenous IS. 3. Reosorbilact is the main component of IDT in any IP, as it affects the main links of the pathogenesis of the latter.

Background. The microcirculatory system (MCS) is a network of blood vessels that includes arterioles, capillaries, venules, and terminal lymphatic vessels. Microcirculation is characterized by the constant variability. Factors of atherogenesis development due to MCS dysfunction include shear stress, hyperglycemia, dyslipidemia, systemic and local inflammation, hypoxia and endothelial dysfunction mediated by oxidative stress. Laser Doppler flowmetry (LDF) is used to study microcirculation in the clinical settings. The advantages of LDF include simplicity, accessibility and non-invasiveness. Objective. To describe the features of microcirculation disorders and their elimination. Materials and methods. Analysis of literature data on this topic; own study. The study involved 98 patients (59 females; 39 males) with a mean age of 52.0 years. The first group consisted of patients with coronary heart disease (CHD) and chronic heart failure of I-IIA grades, the second – of relatively healthy individuals. All patients underwent LDF, ultrasound examination of the carotid arteries, and determination of anthropometric parameters. Results and discussion. MCS dysfunction is not only a risk factor for atherogenesis, but also a trigger for its acute complications (myocardial infarction, stroke, sudden death). Nitric oxide (NO) deficiency plays an important role in this. A potential target of therapeutic influence in the treatment of coronary heart disease is not only macrovascular system, but also vasa vasorum. The condition of the latter determines the course of atherosclerosis. According to the results of our own study, patients with CHD demonstrated a muscle mass decrease, an increase in waist and hip circumference, and in body mass index. In addition, the groups differed in thickness of the intima-media complex of both common carotid arteries (right common carotid artery: CHD group – 0.79±0.18 mm; group of relatively healthy individuals – 0.69±0.13 mm, p<0,05; left common carotid artery: CHD group – 0.81±0.19 mm, group of relatively healthy individuals – 0.70±0.14 mm, p<0,05). When assessing the indicators of wavelet analysis of LDF, a significant decrease in the rate of microcirculation and capillary blood flow reserve is revealed in the CHD group, as well as an increase in peripheral vascular resistance. According to previous own studies, sorbitol (Reosorbilact, “Yuria-Pharm”) and pentoxifylline (Latren, “Yuria-Pharm”) can be used to correct microcirculation disorders. The use of these drugs leads to vasodilation of precapillary sphincters and improvement of regional microperfusion. Conclusions. 1. Disorders of MCS are the pathogenetic factors of the atherogenesis. 2. Laser Doppler flowmetry is used to study microcirculation in the clinical settings. 3. In patients with CHD there is an increase in neuro- and myotonus of the MCS, which is associated with the impaired release of nitric oxide. 4. Changes in microcirculation contribute to the development of atherosclerosis, which should be taken into account when choosing treatment for such patients. 5. Sorbitol (Reosorbilact) and pentoxifylline (Latren) can be used to correct microcirculation disorders.

Background. For hospital pharmacists and nurses it is critical to have real data about the stability of injectable drugs in practical situations: opened drug formulation, after the reconstitution of lyophilized production or after the dilution in various vehicles. Unfortunately, these data are seldom available. The manufacturer’s stability data are usually quoted as “stable for 24 hours at 4 °C” not for the true reasons, but considering the possible bacterial contamination or due to the fact that stability tests were only conducted during a very short period. This problem is of paramount importance for therapeutic proteins, mainly monoclonal antibodies, because the latter are very expensive. Objective. To define the in use stability of anticancer drugs. Materials and methods. Analysis of literature data on this topic; own study on diluted rituximab stability. Results and discussion. Biologic drugs have revolutionized the treatment and prevention of many debilitating and life-threatening diseases. Biologics are much bigger and have a much more complicated structure than classical drugs. Principal causes of biologics’ instability include temperature changes, dilution, absorption, oxidation, shaking and shearing etc. Protein instability can be divided into physical and chemical instability. The former includes aggregation, denaturation and absorption on surfaces, and the latter – desamidation, disulfide bonds breakage and formation, oxidation, hydrolysis, isomerization, non-disulfide cross-linking, and deglycosylation. Instability of anticancer drugs and biologicals can lead to their toxicity, immunogenicity and efficacy loss. Instability can be overcome by the centralization of pharmacy handling, but firstly it needs to be thoroughly studied with the help of modern methods. The own study has revealed that the diluted rituximab is stable up to 6 months in polyolefin bags stored at 4 or 22 °C. The preparations can be realized without any problems. There also no fear of instability in case of thermal excursions. Such findings if introduced in practice can save about 150,000 euros a year. Conclusions. 1. In-use analysis of proteins requires several methods. 2. Instabilities are divided into physical and chemical. 3. Aggregation is an initial response to any stress and must be completely eliminated.

Background. Diabetic foot syndrome (DFS) is the presence of an infection and/or ulcer defect of the foot associated with neuropathy and circulatory disorders of the lower extremities of varying severity. Insensitivity of the foot, its deformation and constant load lead to the formation of necrosis under hyperkeratosis with the potential infectious process development. Objective. To describe the features of the course and treatment of DFS. Materials and methods. Analysis of literature data on this issue. Results and discussion. Classification of diabetic ulcers is carried out according to the PEDIS system, where P means perfusion, E – extent, D – depth, I – infection, S – sensation. To assess the circulatory status of the lower extremities, the ankle-brachial index (ABI) and transcutaneous oxygen tension are determined. Critical ischemia is determined by the following criteria: tibial systolic blood pressure <50 mm Hg, big toe blood pressure <30 mm Hg, or transcutaneous oxygen tension <30 mm Hg, or ABI <0.5. DFS treatment involves unloading the foot with the help of special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, surgery, antibiotic therapy. If necessary, anti-pseudomonad antibiotics should be used (ceftazidime, cefoperazone, cefepime, imipenem, meropenem, ciprofloxacin, amikacin). 95 % of the microorganisms present in the world are able to coexist in the form of biofilms – communities of microorganisms in a matrix of polymers (mucopolysaccharides), which are released by the same bacteria. Taking this into account, one should choose antibiotics that can penetrate biofilms. Diabetic ulcers should be covered with dressings such as Hydroclean plus, which contain an antiseptic that protects the wound from secondary infection, prevents excessive evaporation of moisture and has an atraumatic contact layer that prevents traumatization of the young granulation tissue. This dressing continuously releases Ringer’s solution into the wound and absorbs the wound exudate, creating a continuous washing effect. Lacerta (“Yuria-Pharm”) can be used to stimulate the regeneration of long-term defects of connective tissues. Lacerta activates the migration and proliferation of fibroblasts, accelerates their metabolic activity, and enhances angiogenesis. Other methods of accelerating of the wound healing include the use of cryopreserved amniotic membranes and the injection of stem cells. Conclusions. 1. DFS is the presence of an infection and/or ulcerative defect of the foot associated with neuropathy and circulatory disorders of the lower extremities. 2. Classification of diabetic ulcers is carried out according to the PEDIS system. 3. Treatment of DFS involves unloading the foot with special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, antibiotic therapy, surgery. 4. It is advisable to cover diabetic ulcers with hydrogel bandages. 5. Lacerta can be used to stimulate the regeneration of persistent skin defects.

Background. Personal protective equipment (PPE) is an item of clothing designed to protect healthcare workers (HCW) or others from infection. PPE includes gloves, masks, gowns, respirators, goggles, face shields, headgear, boot covers, rubber shoes, and more. Objective. To describe the evolution of medical devices for HCW protection. Materials and methods. Review of literature data on this issue. Results and discussion. Medical gloves are divided into sterile and non-sterile. The purpose of wearing non-sterile gloves is to prevent contamination of the hands of HCW with microorganisms. They should be worn when there is a risk of contact with blood or other body fluids, patient secretions, or contaminated equipment. Gloves do not protect against contamination and after their use it is still necessary to treat hands with antiseptic. Latex gloves have good elasticity and flexibility, are convenient and anatomically suitable for hands, have a good sensitivity to touch. However, they can cause allergies or skin irritation. Latex allergy is the most common cause of perioperative anaphylaxis in children. It is recommended to use powder-free gloves. Nitrile gloves for examination manufactured by “Yuria-Pharm” are characterized by high toughness, elongated cuff, and special texture facilitating holding the instruments. Surgical masks consist of three layers of thermoplastic polymer located between the layers of nonwoven fabric. They are designed to protect against pathogens (mainly bacteria) transmitted in large droplets (>5 μm). The Cochrane review did not show any convincing effect of wearing of surgical masks on reducing the risk of infectious complications during sterile surgical procedures. WHO recommends wearing surgical masks to prevent the transmission of coronavirus disease (COVID-19). N95 or FFP3 class respirators are recommended for aerosol-generating procedures (tracheal intubation, bronchoscopy) and for dangerous infections. N95 respirators are the standard for working with patients with COVID-19 in USA. They can be with a valve or without it. These respirators consist of thermoplastic polymer and nonwoven fabric and filter 95 % of particles sized ≥0.3 μm. They should tightly fit to the face and be tested for leaks before the contact with patient. A similar tactic should be used when wearing FFP3 respirator. Valve respirators are easier to use because the presence of a valve facilitates exhalation. The valve also increases comfort and prevents excessive accumulation of moisture under the respirator. Such respirators do not filter the exhaled air, so they do not protect others from infection. Another field of PPE application is its usage in hematocontact infections caused by hepatitis B/C virus and human immunodeficiency virus. The risk of HCW infection is associated with pricks, cuts, contact with the patient’s body fluids, and any invasive diagnostic or treatment procedures. The risk of patient’s infection is present in case of the improper instruments sterilization, use of non-sterile infusion solutions, transfusion of blood and its components, transplantation, and contact with biological fluids of the infected HCW. To reduce the risk of HCW infection, always wear gloves if there is a risk of contact with blood or other body fluids; never put the cap on the needle after using it; always keep a container for sharp objects on hand; carry out the necessary vaccinations; use PPE and safety needles, scalpels and syringes. Conclusions. 1. Wearing masks reduces the risk of COVID-19 transmission. 2. During aerosol-generating procedures it is necessary to use all available PPE. 3. When wearing a respirator, it is advisable to check its tightness. 4. The number of extra injections should be minimized.

Background. Inadequate volume of perioperative infusion therapy (IT) is one of the predictors of postoperative complications. There are different types of infusion solutions on the pharmaceutical market: albumin, dextrans (Reopoliglukin), polyatomic alcohols (Reosorbilact, Sorbilact), hydroxyethyl starch preparations (Gekodez), modified gelatin (Volutenz), balanced colloid-hyperosmolar solution (Gekoton), etc (all listed solutions are produced by “Yuria-Pharm”). Objective. To describe the main features of perioperative IT. Materials and methods. Analysis of literature sources on this topic. Results and discussion. Inadequate IT can cause hypo- and hypervolemia, as well as slow the recovery after surgery, so the choice of infusion solution should be made very carefully. To eliminate endothelial dysfunction, which often accompanies the perioperative period, it is advisable to prescribe L-arginine (Tivortin, “Yuria-Pharm”), which acts as a substrate for the synthesis of nitric oxide. Tivortin has the following properties: membrane stabilizing, antioxidant, cytoprotective, detoxifying, endothelioprotective, anabolic, hepatoprotective, antihypoxic. L-arginine (Tivortin) also helps to correct acid-base balance, neutralizes and removes ammonia, promotes insulin synthesis and regulates blood glucose, reduces the activation and adhesion of leukocytes and platelets to the vascular endothelium. The position paper of the International Fluid Optimization Group (2015) states that in planned operations without blood loss, crystalloids can be prescribed (2 ml/kg/h for surgeries lasting >4 hours, up to 10 ml/kg/h for surgeries lasting up to 1 hour). However, the disadvantages of the most famous crystalloid (0.9 % saline) are the risk of hyperchloremic acidosis and the development of edema in case of overdose, so it is advisable to use ion-balanced solutions instead of 0.9 % NaCl. The ideal electrolyte solution should be isovolemic, isohydric, isooncotic, isoionic, and isotonic to the blood plasma. Elimination of the metabolic acidosis is an important task of perioperative IT. Soda-Bufer (“Yuria-Pharm”) can be used for this purpose, as the administration of sodium bicarbonate reduces mortality in patients with severe metabolic acidosis and acute kidney damage. To eliminate the intoxication syndrome, drugs of polyatomic alcohols (Reosorbilact) have been successfully used. Efficiency of Reosorbilact in the treatment of sepsis, peritonitis, pneumonia, burns, etc. was confirmed in the numerous studies. In addition to detoxification, Reosorbilact supports hemodynamics and microcirculation, corrects metabolic acidosis and water-electrolyte disorders, stimulates diuresis, normalizes the rheological properties of blood, which makes it the main drug for low-volume IT in the perioperative period. In turn, Xylate is the main solution in diabetes because it has antiketogenic and lipotropic properties, improves hemodynamics and microcirculation, corrects metabolic acidosis and has an osmodiuretic effect. In shock settings IT should be administered according to the ROSE concept (R (rescue) – aggressive IT; O (optimization) – support of tissue perfusion; S (stabilization) – supportive IT; E (evacuation) – deresuscitation, restoration of body functions). Conclusions. 1. Optimal IT improves the consequences of the surgery. 2. To eliminate endothelial dysfunction, it is advisable to prescribe L-arginine (Tivortin). 3. Reosorbilact is successfully used to eliminate the intoxication syndrome, which also supports hemodynamics and microcirculation, corrects metabolic acidosis and water-electrolyte disorders, which makes it the main drug for low-volume IT in the perioperative period. 4. Xylate is the main solution in diabetes because it has antiketogenic and lipotropic properties, improves hemodynamics and microcirculation. 5. In shock settings IT should be administered according to the ROSE concept (rescue, optimization, stabilization, evacuation).

Background. Infusion therapy (IT) is one of the main methods of drug therapy optimization. The essence of IT is to correct homeostasis disorders in order to detoxify, to restore the disrupted microcirculation and tissue perfusion, to eliminate the disorders of rheological and coagulation blood properties, to eliminate metabolic disorders, to improve drug delivery to the pathological focus, to restore circulating blood volume, to normalize fluid and electrolyte and acid-base balance. Objective. To describe modern IT. Materials and methods. Analysis of the literature sources on this topic. Results and discussion. Requirements for modern plasma substitutes include safety, sufficient and long-lasting volemic effect, rapid renal excretion, lack of accumulation and effect on the coagulation system, maximum similarity to blood plasma, and availability. There are several classes of plasma substitutes, and each of them has its own indications. For example, crystalloids are prescribed for dehydration, and colloids – for hypovolemia. The infusion volume is calculated based on the physiological needs of the organism, taking into account pathological fluid loss (fever, shortness of breath, postoperative wound drainage, vomiting, polyuria). Endogenous intoxication (EI) – a pathological condition that occurs as a result of exposure to toxic substances of exogenous or endogenous nature, which cause dysfunction and the development of extreme conditions – is an important field of IT application. EI can accompany chronic heart failure, peripheral vessels atherosclerosis, autoimmune and allergic diseases. Toxins have a direct (direct destruction of proteins and lipids, blocking of synthetic and oxidative processes in the cell) and indirect (microcirculation system and vascular tone disorders, changes of blood rheological properties) adverse effects. Clinical manifestations of EI include fever, malaise, and the dysfunction of various internal organs. As EI depletes the natural mechanisms of detoxification, worsens the clinical course of the disease, reduces drug sensitivity, suppresses immunity, it is an indication to detoxification via infusion. The tasks of the latter are to improve tissue perfusion, to provide hemodilution with a decrease in the toxins’ concentration, to stimulate diuresis, to eliminate acidosis, and to maintain the functional state of hepatocytes. For this purpose, solutions of polyatomic alcohols (Reosorbilact, Xylate, “Yuria-Pharm”) can be used. Reosorbilact increases the circulating blood volume, improves microcirculation and rheological blood properties, increases tissue perfusion, promotes “wash-out” of toxins, corrects acidosis and fluid and electrolyte balance, normalizes hepatocyte function, improving the own detoxification mechanisms. In case of microcirculation disturbances, it is reasonable to use the combined IT with the inclusion of Reosorbilact, Latren and Tivortin (“Yuria-Pharm”). Latren increases the elasticity of erythrocytes, reduces the aggregation of erythrocytes and platelets, normalizes the electrolyte composition of blood plasma, and Tivortin acts as a substrate for the formation of nitric oxide – the main signaling molecule of the endothelium. In addition to EI, IT usage is often prescribed for diabetic ketoacidosis. In such cases, it is advisable to use Xylate (“Yuria-Pharm”), which has antiketogenic properties, improves hemodynamics, corrects acidosis, and does not increase blood glucose levels. Xylate is recommended to be used only after preliminary rehydration with the help of isotonic saline solutions. Conclusions. 1. IT is an important method of treating a number of diseases. 2. EI accompanies not only diseases that involve intoxication syndrome, but also almost all internal diseases. 3. Reosorbilact and Xylate are the optimal solutions for detoxification. 4. It is reasonable to use combined IT, for example, the combination of Reosorbilact with Latren and Tivortin.

Background. Anemia is a decrease in the number of erythrocytes and hemoglobin levels as a result of blood loss, disruption of erythropoietic cell production, and increased erythrocyte breakdown or a combination thereof. Anemia of pregnant women is divided into physiological anemia and pathological conditions. In case of latent iron deficiency clinical manifestations are absent. This condition is characterized by a decrease in iron and erythropoietin to a level sufficient to maintain hematological parameters at the lower limit of normal values. In the absence of iron supplements administrations 65 % of cases of latent deficiency end up in a manifest deficiency. Objective. To describe the features of the anemia treatment in inpatient settings. Materials and methods. Analysis of literature sources on this issue. Results and discussion. The normal value of hemoglobin for the 1st and 3rd trimesters is ≥110 g/l, for the 2nd – ≥105 g/l. After childbirth, anemia is determined as a decrease in hemoglobin <100 g/l. Risk factors for anemia in pregnant women include poor nutrition, chronic diseases, chronic intoxication, history of anemia, bleeding during pregnancy, multiple pregnancy, frequent childbirth with a long lactation period, and short intervals between births. Anemia in pregnant women increases the probability of premature birth by 63 %, of low birth weight – by 31 %, of perinatal mortality – by 51 %, of neonatal death – in 2.5 times. In case of maternal anemia, the newborn has a worse development of external respiratory function, a lag in the weight gain and a greater susceptibility to infectious diseases. To diagnose anemia, a general blood test and determination of additional indicators (serum iron, ferritin, ferritin saturation, transferrin, soluble ferritin receptor) are used. Patients with mild anemia do not require hospitalization; patients with moderate anemia need hospitalization in the absence of a response to oral iron supplements; patients with severe anemia need hospitalization after the mandatory consultation of hematologist. The purposes of anemia treatment include the normalization of blood tests, correction of iron deficiency, and the creation of iron stores to ensure full fetal development and lactation. Evaluation of treatment is performed on the 21st day after treatment; normally the increase in hemoglobin is about 1 g per 1 day of therapy. If hemoglobin has increased by <10 g/l, it is advisable to prescribe intravenous iron. Indications for parenteral administration also include the intolerance to oral iron supplements, peptic ulcer disease in the exacerbation phase, lack of confidence in the good adherence of the patient, hemodialysis, swallowing disorders, and the need for a more pronounced increase in hemoglobin. If it is necessary to quickly restore the level of blood hemoglobin in the late stages of pregnancy, Sufer (“Yuria-Pharm”) can be administered (10.0 ml in 200.0 ml of saline intravenously 1-3 times a week). Parenteral administration of iron supplements should be administered with caution in case of polyvalent allergies, active infections, chronic liver disease, and signs of iron overload. Parenteral administration of iron supplements is not indicated in the 1st trimester of pregnancy. Conclusions. 1. Anemia in pregnant women increases the likelihood of premature birth, low birth weight, perinatal mortality, and neonatal death. 2. The purposes of anemia treatment are the normalization of blood tests, correction of iron deficiency and the creation of iron stores. 3. Indications for parenteral administration of iron are lack of response and intolerance to oral iron supplements, exacerbation of the peptic ulcer disease, and the need for a more pronounced increase in hemoglobin. 4. If it is necessary to quickly restore the level of hemoglobin in the late stages of pregnancy, Sufer may be prescribed.

Background. Treatment of blood malignancies is often accompanied by the hematological toxicity. Thrombocytopenia is one of the most common phenomena, which can be caused by pseudothrombocytopenia, production deficiency or increased destruction of platelets, their pathological distribution or aggregation. Objective. To determine the features of hematological toxicity in the treatment of malignant blood diseases. Materials and methods. Analysis of literature data and recommendations on this topic. Results and discussion. Diagnosis of thrombocytopenia involves a detailed study of a peripheral blood smear to assess the morphology of all cells, as well as additional studies (determination of lactate dehydrogenase, D-dimer, fibrinogen, etc.; aspiration and bone marrow biopsy; virological and bacteriological studies; clinical examination). The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. Emaplag is indicated for the treatment of thrombocytopenia caused by ChT in patients with solid tumors, patients with platelet counts <50×109/L, and in cases where the physician decides to increase platelet count. With regard to anemias, their main causes in cancer patients are the factors of the underlying disease (bone marrow infiltration, infectious processes), the impact of ChT or RT, other causes (malnutrition, bleeding, renal dysfunction). Examination of patients with anemia should include history taking, evaluation of blood smear and iron metabolism, exclusion of occult gastrointestinal bleeding and renal failure, Coombs’ test, determination of endogenous erythropoietin. Treatment options for ChT-induced anemia include blood transfusions and the use of erythropoietins (epoetins α and β, darbepoetin) with or without iron supplements (oral or intravenous). The advantages of using erythropoietin include reducing the need for transfusion of erythrocyte mass, a gradual increase in hemoglobin, increasing quality of life. However, erythropoietins are not recommended for use in cancer patients who do not receive ChT or receive RT, because in these cases, their use is associated with an increased mortality risk. Because in some patient groups erythropoietins accelerate tumor growth or reduce survival, the patient must give a written informed consent for their use. Given these data, it is advisable to prescribe intravenous iron, as it allows not only to quickly increase hemoglobin and improve quality of life, but also to reduce the dosage of erythropoietins. Iron carboxymaltose if the most modern parenteral iron preparation. It is characterized by low toxicity and high stability. Conclusions. 1. Thromboconcentrate transfusion is a fast and effective way to correct thrombocytopenia, which has a number of disadvantages. 2. Thrombopoietin receptor agonists (eltrombopag) make it possible to increase the effectiveness of treatment without interrupting the planned therapy. 3. In the presence of anemia, all possible causes should be corrected before prescribing erythropoietins. 4. If the anemia is caused by ChT, the patient needs to take erythropoietins. 5. Addition of intravenous iron preparations to erythropoietin therapy significantly increases the effectiveness of treatment.

Background. Peritonitis is a consequence of complications of the abdominal cavity organs’ diseases (inflammation, injury) and systemic inflammatory reaction of the organism, which is manifested by symptoms of intoxication and dysfunction of all the organs. In case of diffuse peritonitis mortality is about 80 %. Prerequisites of the lethal outcomes include a late visit to the doctor, elderly age, the presence of cancer and diabetes, antibiotic resistance of the pathogen, diagnostic errors. In the department of purulent gynecology peritonitis most often accompanies endometritis, purulent salpingitis, pyosalpinx, abscesses, uterine perforation during curettage. In Moldova, the principles of treatment of peritonitis include the urgent surgery to remove the infection source, aspiration of exudate, massive lavage, abdominal drainage, antibiotic therapy, and correction of metabolic disorders. Objective. To determine the effectiveness of Reosorbilact in eliminating the intoxication syndrome in peritonitis. Materials and methods. The Rheo-STAT study was an international multicenter, randomized, open-label clinical trial of the efficacy and safety of Reosorbilact (“Yuria-Pharm”) in the treatment of sepsis, peritonitis, community-acquired pneumonia, and burn disease. The study was conducted in 7 countries (Ukraine, Moldova, Georgia, Vietnam, Kazakhstan, Kyrgyzstan, Uzbekistan). 5 of them (Ukraine, Moldova, Georgia, Kazakhstan, Uzbekistan) took part in the sub-study Rheo-STAT Peritonitis. The study involved 628 adult patients with sepsis, peritonitis, pneumonia and burns. The subgroup of peritonitis consisted of 180 people (27 % males, 73 % females; mean age – 37 years; concomitant infectious diseases were observed in 25 %, complicated appendicitis – in 17 %), 117 of them were treated in Moldova (87 % females, 13 % males, mean age – 45.2 years). The inclusion criteria were age 18-60 years, diagnosis of peritonitis, the first hours of the postoperative period, no later than 24 hours from diagnosis to the first visit of the study, obtaining informed consent, baseline level on the SOFA scale ≥2. The total score on the SOFA scale on day 3 of treatment compared to baseline was considered a primary endpoint. Secondary endpoints were the change in the overall score on the APACHE II, SAPS II, MODS, PSI/PORT, CURB-65 scales; changes in biochemical, immunological and integral markers of endogenous intoxication. Results and discussion. Low-volume infusion therapy with Reosorbilact (200-400 ml per day) resulted in an increase in circulating blood volume and a decrease in the total volume of infusions required without the risk of volume overload. Exogenous lactate in Reosorbilact did not increase the content of endogenous lactate, which indicates the high safety of the drug. The inclusion of Reosorbilact in the comprehensive treatment after 3 days provided a decrease in body temperature from 37.1 to 36.75 °C, heart rate – from 88.5 to 82.0 bpm, the leukocyte count – from 11.0 to 7.2×10⁹/L. Reosorbilact therapy in 3 days improved the acid-base balance, as evidenced by the increase in the base excess from -2.73 to -0.57 mmol/L and an increase in standard bicarbonate from 21.8 to 23.5 mmol/L. Conclusions. 1. Prerequisites for the lethal consequences of peritonitis include a late visit to the doctor, elderly age, the presence of cancer and diabetes, antibiotic resistance of the pathogen, and diagnostic errors. 2. Elimination of intoxication syndrome is one of the main components of peritonitis treatment. 3. Reosorbilact infusion therapy increases the volume of circulating blood without the risk of volume overload. 4. The inclusion of Reosorbilact into the comprehensive treatment of sepsis after 3 days provided a decrease in body temperature, heart rate, white blood cell count and normalization of the acid-base composition of the blood.

Background. Dorsopathy is a group of diseases of the musculoskeletal system and connective tissue associated with degenerative diseases of the spine. Risk groups for the development of dorsopathies include people with a sedentary lifestyle, people working in difficult conditions, athletes, military personnel, people with obesity. Clinical classification of dorsopathies involves their division according to the affected level (cervical, thoracic, lumbosacral). Objective. To describe the management of patients with back pain. Materials and methods. Analysis of literature data on this topic. Results and discussion. Cervicocranialgias, related to dorsopathies, include vertebral artery syndrome (VAS) and extravasal artery compression (EAC). VAS is a complex of cerebral, vascular and autonomic disorders that occur due to the damage of the sympathetic plexus of vertebral artery, deformation of the wall or changes in its lumen. In turn, EAC involves the compression of blood vessels by bone abnormalities, muscles, osteophytes of the cervical vertebrae, scars, tumors, and so on. Lower back pain (LBP) is one of the most common dorsopathies. Its prevalence has doubled in the last decade. The mechanism of aseptic inflammation in dorsopathies includes such links as the release of proinflammatory mediators, activation of peripheral nociceptors, production of cyclooxygenase-2 and the formation of prostaglandins. Pain in dorsopathies is classified into nociceptive (caused by the excitation of nociceptors in damaged tissues), neuropathic (caused by damage to the central or peripheral nervous system) and psychogenic (caused by primary mental disorders). By duration, LBP is classified into acute (3 months). According to the etiology, the following subspecies are distinguished: radicular (disc herniation, spondylosis, vertebral canal stenosis), specific (cancer, infection, fracture, equine tail syndrome) and nonspecific (myogenic disorders, facet syndrome). In the presence of so-called symptoms of red flags, it is recommended to conduct imaging examinations according to the indications. Such symptoms include pain development at the age of 55 years, recent back injury, progressive character, deterioration or lack of dynamics after keeping horizontal position, prolonged use of glucocorticoids, history of malignant tumors, osteoporosis, intravenous drugs injection, immunodeficiency, weight loss, fever, focal neurological symptoms, pain on palpation of the spine, spinal deformity. The symptoms of yellow flags predict pain chronization. The latter include certain work-related circumstances, beliefs, behaviors, and affective symptoms. The main causes of non-specific back pain include muscular-tonic pain syndrome (MTPS), myofascial pain syndrome (MFPS), arthropathies. Microcirculatory disorders, caused primarily by the reflex muscle spasm, play a significant role in the development of pain in these conditions. MTPS develops on the background of degenerative-dystrophic changes in the spine, ligaments and muscles as a result of exposure to provoking factors (significant physical exertion, injuries, sudden movements, prolonged stay in a static position, general or local hypothermia). Chronization of MTPS leads to the development of MTFS. Ischemic muscle spasm leads to the spasm of arteries and dilation of venules with impaired microcirculation and accumulation of inflammatory mediators. In turn, radicular ischemia develops with radicular pain. Venous plexus, which is compressed at the stage of stenosis without signs of direct compression of the root, is the most vulnerable structure of the intervertebral space. Treatment of LBP includes bed rest, sleep on a hard surface, the use of non-specific anti-inflammatory drugs, local administration of local anesthetics, muscle relaxants, B vitamins, therapeutic exercises and surgical treatment. Restoration of microcirculation makes it possible to influence the pathogenesis of radiculoischemia. Drugs that improve microcirculation and hemodynamics are included in the domestic clinical protocol for the treatment of dorsalgia. Reosorbilact (“Yuria-Pharm”) improves substance exchange between blood and tissues and helps to remove metabolic products. These effects are based on the opening of precapillary sphincters on the background of this solution use. For dorsalgia, it is also advisable to prescribe Latren (“Yuria-Pharm”) – a combination of pentoxifidine and Ringer’s lactate. Latren inhibits the aggregation of blood cells, increases the elasticity of erythrocytes, promotes vasodilation, normalizes the electrolyte composition of blood plasma. To eliminate endothelial dysfunction, Tivortin (“Yuria-Pharm”) is prescribed, which promotes vasodilation. The use of the listed above infusion drugs influences the pathogenesis of the process, eliminating dorsalgia. Conclusions. 1. LBP is one of the most common dorsopathies. 2. Pain in dorsopathies is classified into nociceptive, neuropathic and psychogenic. 3. Microcirculatory disorders play a significant role in the development of nonspecific LBP. 4. Combined use of Reosorbilact, Latren and Tivortin influences the pathogenesis of the process, eliminating dorsalgia.

Background. Experience in high-risk obstetrics shows that a significant part of the determining factors affects the woman and the fetus before the first visit to the doctor. Improving a woman’s health before conception can improve her reproductive performance and reduce financial costs spent on obstetric medical aid. Objective. Describe the key concepts of preconception training. Materials and methods. Analysis of literature sources on this topic; own study involving 42 pregnant women (22 women with systemic lupus erythematosus (SLE), 20 women with congenital heart disease (CHD) and hypertensive complications of previous pregnancies), who were divided into two groups. Group 1 received routine drugs and L-arginine (Tivortin, “Yuria-Pharm”) in doses recommended for cardiac patients, and group 2 – only routine drugs. Results and discussion. The components of preconception programs include the individual responsibility of women throughout life, awareness of women, preventive visits, interventions on identified risks, pre-pregnancy examinations and pregnancy supervision, health insurance for low-income women, health programs and strategies, medical research, and the improvement of monitoring. Target groups of preconception include women with unfavorable obstetric history (premature birth, cessation of fetal development, cesarean section, stillbirth, multiple miscarriages, birth of children with birth defects, hypertensive complications of pregnancy) and chronic diseases (type 1 diabetes mellitus, SLE, antiphospholipid syndrome, severe cardiovascular pathology, arterial hypertension, pulmonary hypertension). An important role in the management of pregnant women belongs to the prevention of preeclampsia (PE). Administration of acetylsalicylic acid reduces the likelihood of PE by 10 % in low-risk pregnant women and by 25 % in high-risk pregnant women, but the drug should be started during gestation. The use of calcium (1000 mg) reduces the risk of PE in high-risk pregnant women by 37 %. Preconception preparation is especially important, because some processes, such as the implantation of placental structures, begin and end before a woman learns she is pregnant. Remodeling of the spiral arteries also begins in the early stages of pregnancy, so its correction after the confirmation of pregnancy is less effective than prevention before it occurs. E.E. Camarena Pulido et al. (2016) studied the role of L-arginine (5 tablets of 600 mg per day from the 20th week of gestation before delivery) in the prevention of PE in high-risk women. In the L-arginine group significantly fewer cases of PE (3/49 vs. 11/47 in the placebo group; p=0.01) and a lower incidence of preterm birth were detected. In the another study, pregnant women with chronic hypertension received oral L-arginine or placebo. In the arginine group, there was a lower need for antihypertensive drugs, as well as lower frequency of births before 34 weeks, PE and neonatal complications (Neri I. et al., 2010). In the own study, favorable obstetric results of Tivortin were found. The percentage of births at >37 weeks in the Tivortin group among women with SLE was 90.9 %, and in the group of standard therapy – 50 % (p<0.01), among women with CHD – 90 % and 75 % respectively; p<0.05). No newborns with an Apgar score of <7 were found in the Tivortin group. In the comparison group their number was 27.7 %. Laboratory studies have shown that there is a significant increase in endothelial progenitor cells in the Tivortin group. Conclusions. 1. Preconception preparation of pregnant women is a multifaceted set of measures. 2. A significant number of physiological and pathological processes occur in the early stages of pregnancy, so they can be influenced only in the preconception period. 3. The use of L-arginine during gestation reduces the risk of PE, premature birth and other complications in all women and especially in women with hypertension.

Background. Impaired drug absorption is one of the reasons of the ineffectiveness of tuberculosis (TB) treatment. Malabsorption syndrome (MS) is a clinical syndrome that occurs due to the impaired digestive and transport function of the small intestine and is characterized by impaired absorption of nutrients, vitamins, microelements and drugs from the digestive tract. MS accompanies the following pathological conditions: pancreatic diseases, cholestasis, inflammatory bowel diseases, autoimmune enteropathies, diabetes mellitus, amyloidosis, hyperthyroidism, atrophic gastritis, HIV/AIDS, infections and parasitosis of the digestive system, alcoholism, and TB. Objective. To describe the ways to overcome the influence of MS on TB treatment. Materials and methods. Analysis of literature data on this topic. Results and discussion. MS can worsen the treatment of all forms of TB, especially severe. The latter include tuberculous meningitis, disseminated TB, miliary TB, caseous pneumonia, and infiltrative TB. Causes of death from severe forms of TB include untimely diagnosis, lack of thorough differential diagnosis, insufficient intensity of therapy, decreased maximum concentration of oral forms of anti-TB drugs (ATBD) in blood. The latter often occurs in severe forms of TB and in case of co-infection with TB and HIV/AIDS. Injectable forms of the drugs are recommended by the World Health Organization to increase the effectiveness of TB meningitis treatment. The American Thoracic Society and the American Society of Infectious Diseases also recommend the use of intravenous ATBD in patients with impaired absorption. Most patients receiving oral ATBD have extremely low plasma concentrations of these drugs. This is probably due to a decrease in the functional area of intestinal absorption in patients with TB. Indications for intravenous ATBD include severe forms of TB, the presence of severe disorders of the digestive system and severe comorbidities, TB with multiple and widespread resistance to ATBD, pre- and postoperative periods, low adherence to therapy. The intensive phase of therapy and the patient’s preference may be the additional indications. Studies show that intravenous ATBD is associated with significantly better survival than oral, in the absence of an increase in the number of side effects. The advantages of intravenous administration also include 100 % bioavailability, 100 % controllability of treatment, intensification of therapy, overcoming and preventing the development of resistance of mycobacteria, reducing the risk of adverse reactions, improving the tolerability of chemotherapy. Conclusions. 1. Impaired drug absorption is one of the reasons for the ineffectiveness of TB treatment. 2. MS can worsen the treatment of all forms of TB, especially severe. 3. In patients with malabsorption it is recommended to use intravenous ATBD. 4. Intravenous ATBD is associated with significantly better survival than oral, in the absence of an increase in the number of side effects.

Background. An analysis of 44,415 Chinese patients with COVID-19 found a critical condition defined as severe hypoxemia and/or other organ damage or shock in 2087 (5 %) (Wu Z. et al., 2020). In inpatients, the frequency of shock is likely to be higher and can reach 20-35 % (Yang X. et al., 2020). Risk factors for shock and unstable hemodynamics in COVID-19 are older age, the presence of comorbidities, lymphopenia, higher levels of D-dimer. Objective. To describe the features of infusion therapy (IT) in patients of the therapeutic profile during the COVID-19 pandemic. Materials and methods. Analysis of literature sources on this topic. Results and discussion. The Surviving Sepsis guidelines state that crystalloids, not colloids, should be used for acute resuscitation of patients with COVID-19. The recommendation is based on indirect data on critically ill patients (Cochrane review by S.R. Lewis et al.). It is advisable to use buffered/balanced crystalloids. Such solutions include Reosorbilact (“Yuria-Pharm”), which has such effects as hemodynamic, detoxifying, microcirculatory, and diuretic. Reosorbilact corrects fluid-electrolyte and acid-base balance, improves the rheological properties of blood, reduces the need for sympathomimetics. The use of hydroxyethyl starch, gelatin and albumin in COVID-19 is not recommended. In the treatment of coronavirus pneumonia, IT is significantly limited due to the risk of fluid overload and the development of pulmonary edema. The use of conservative rather than liberal IT strategy is recommended, including for patients with acute respiratory distress syndrome (ARDS) who are on mechanical lung ventilation (MLV). In severe pneumonia, the use of vasopressors is recommended. Noradrenaline is used as a first-line vasoactive agent. The use of hyperosmolar solutions reduces the volume of infusion required to maintain stable hemodynamics in patients with severe sepsis. Hypertonic solutions also reduce the length of MLV in patients with shock. For adults with COVID-19 and refractory shock, low-dose corticosteroid therapy (bolus doses or infusion of prednisolone at a dose of 200 mg per day) has been suggested. Systemic corticosteroids should also be used in ARDS. In the absence of the latter, routine use of systemic corticosteroids is not recommended. Empirical use of antibacterial drugs is advisable in patients on ARDS, as superinfections in this group of patients are extremely common. The advantages of levofloxacin (Leflocin 750, “Yuria-Pharm”) include high efficiency against all respiratory pathogens, good penetration into the inflammatory focus, and active influence on microorganisms in biofilms. Leflocin 750 mg is administered once a day intravenously for 5-14 days. It is recommended to use paracetamol (Infulgan, “Yuria-Pharm”) to control fever. The advantages of the latter are lowering the temperature within 30 minutes after administration, antipyretic effect lasting up to 6 hours, safety for patients with gastrointestinal and hematological diseases. Infulgan is administered intravenously (1 g up to 4 times a day). Conclusions. 1. Balanced IT holds a leading position in the treatment of severe coronavirus infection. 2. Preference should be given to balanced solutions of crystalloids. 3. The IT program should be designed taking into account the quality of life and creating maximum patient comfort.

Background. About 46.5 million of surgical procedures and 5 million of gastrointestinal endoscopies are performed annually in the United States alone. Each procedure involves contact of the medical equipment with sterile tissues of the patient, so transmission of infection is the main risk of such procedures. Objective. To describe the main errors and dangers in laparoscopic surgery. Materials and methods. Analysis of literature data and own research on this topic. Results and discussion. Endoscopic examinations in gastroenterology can transmit more than 300 types of infections, 70 % of which are salmonella and Pseudomonas aeruginosa. During bronchoscopy 90 types of infections are transferred. Different hospital facilities undergo different decontamination procedures. Objects that penetrate the skin or mucous membranes, or into sterile tissues or the circulatory system, require sterilization. Endoscopes are subject to pre-cleaning, leak testing, manual cleaning, rinsing and disinfection. Ideally, laparoscopes and arthroscopes should be sterilized between procedures in different patients. Such devices are difficult to clean and disinfect due to their complex structure. In the absence of adequate disinfection, infection of the patients occurs in cases where the number and virulence of the introduced bacteria or fungi is sufficient to overcome their own immune defenses. Prevention of infectious complications includes preoperative antiseptic treatment of the operating field and appropriate antibiotic prophylaxis (ABP). Abdominal drainage should be performed only when blood or bile accumulates in the operating field. Regular use of drainage in uncomplicated laparoscopic cholecystectomy (CE) increases the likelihood of infection. Examination of 65 laparoscopic operations for postoperative ventral hernias revealed that the reinforcement of preoperative ABP by the means of 7-day course of fluoroquinolones or cephalosporins significantly reduced the volume and rate of seroma formation. The strategy for the prevention of postoperative complications includes delicate tissue handling, thorough sterilization of instruments, abdominal lavage with Dekasan (“Yuria-Pharm”), the use of broad-spectrum antibiotics, the use of plastic containers for removed organs and pathological formations, etc. In laparoscopic surgery, more than half of intestinal and vascular injuries are the access complication (pneumoperitoneum, the introduction of the first trocar). A significant proportion of such injuries is not diagnosed during injury. Thermal injuries are also possible during laparoscopic interventions. To prevent them, it is advisable to check the instruments for damage, use plastic trocars, use bipolar coagulation methods, use safe methods of dissection and coagulation (ultrasound scissors, vessel sealing technology). The frequency of damage to the bile ducts during laparoscopic CE is 0.26-0.30 %. The author’s study evaluated the effectiveness of laparoscopic subtotal CE in performing technically complex CE. Dekasan was used as an antiseptic for external and intraabdominal lavage during the interventions. Properties of Dekasan are the following: bactericidal, fungicidal, virocidal, sporocidal effects; lack of resorptive action; enhancing of the antibiotics’ effect; reducing the adhesion of microorganisms. In the first period (2005-2008) complex CE (1.5 %) was switched to the open operations. The frequency of postoperative complications was 28 %. In the second period, subtotal CE were used. The average operation time was 95 minutes; the average blood loss was 80 ml. Postoperative complications occurred in 14.6 % of patients. Mortality in the first period was 0.1 %, in the second – 0 %. Conclusions. 1. Endoscopes should be thoroughly disinfected to minimize the risk of infections transmission. 2. Prevention of infectious complications also includes preoperative antiseptic treatment of the operating field and appropriate ABP. 3. In laparoscopic surgery, more than half of intestinal and vascular injuries are the complications of access. 4. Performing laparoscopic subtotal CE is an alternative to conversion in cases where it is impossible to laparoscopically identify anatomical structures.

Background. Bleeding accounts for 34 % of maternal mortality. Every 7 minutes 1 woman dies from bleeding during the labour. Retrospective analysis of medical records shows that in 60-80 % of cases, fatal consequences can be avoided. Criteria for defining the concept of “massive blood loss” are the loss of 100 % of circulating blood volume (CBV) within 24 hours or 50 % of CBV within 3 hours, loss of 150 ml/min, of 2 % of body weight within 3 hours, reduction of hematocrit by 10 % in combination with hemodynamic disturbances, one-time blood loss more than 1500-2000 ml or 25-35 % CBV, the need for transfusion of >10 doses of erythromass for 24 hours. The main causes of bleeding in obstetrics include uterine atony, premature placental abruption, uterine rupture, placental abruption, hereditary blood diseases, coagulopathy, sepsis, amniotic fluid embolism. Objective. To describe infusion therapy (IT) for obstetric bleeding. Materials and methods. Analysis of literature data on this issue. Results and discussion. Strategies for the treatment of obstetric hemorrhage include restriction of the traditional massive crystalloid-based IT, applying the principle of antihypertensive resuscitation, using of adequate doses of tranexamic acid, fibrinogen concentrate and prothrombin complex concentrate, early informed use of blood components, and low-volume IT. Routine use of unbalanced crystalloid solutions in critically severe patients is dangerous. Infusion of large amounts of 0.9 % NaCl may cause metabolic hyperchloremic acidosis. Therefore, except in cases of hypochloremia, it is advisable to replace saline with balanced solutions. Reosorbilact (“Yuria-Pharm”) is the most suitable solution for this purpose. It mobilizes the own fluid of the organism, helping it to move from the intercellular space into the vessels. Hypotensive resuscitation involves the introduction of limited amounts of fluid in the early stages of treatment of hemorrhagic shock (until the bleeding stops). Low-volume IT program is a part of hypotensive resuscitation. In this case, the following solutions can be used: Reosorbilact, Sorbilact, Gekoton (“Yuria-Pharm”), 130/0.4 hydroxyethyl starch (HES), hypertonic NaCl solutions (including combined solutions with colloids), polyhydric alcohols. It should be noted that the new generation of HEC has less effect on coagulation than older drugs. Due to the risk of kidney damage, HEC solutions should be used in the lowest effective dose for as shortest period of time as possible. HEC infusion should be stopped as soon as hemodynamic targets are reached. Solutions containing polyhydric alcohols (Reosorbilact, Sorbilact, Xylate) occupy an important position in IT of critically ill patients. Due to their high osmolarity, Reosorbilact and Sorbilact cause fluid to move from the intercellular space into the vascular bed, improving microcirculation and tissue perfusion. The polyhydric alcohol sorbitol contained in these solutions creates increased osmotic pressure in the renal tubules, which provides a diuretic effect. In case of the blood loss volume of I-II functional class up to 1500 ml and stopped bleeding, IT is performed in a limited mode. The volume of intravenous infusion together with blood components should not exceed 200 % of the blood loss volume. Reosorbilact (10-15 ml/kg) is an initial solution in combination with 0.9 % NaCl (20-30 ml/kg). In case of unstable hemodynamics HEC may be added (up to 1,5 L). Blood components are used only in case of confirmed coagulopathy and continued bleeding. In case of massive critical blood loss >1500-2000 ml, it is advisable to use the protocol of massive blood transfusion 1:1:1:1. In order to reduce the pathological response of the endothelium to IT, it is advisable to use a substrate for the nitric oxide synthesis, namely, Tivortin (“Yuria-Pharm”). To stop life-threatening obstetric bleeding, CBV must be refilled using the protocol of massive blood transfusion and automatic blood reinfusion, oxytocin and prostaglandin analogues for the correction of uterine tone, uterine massage, correction of coagulopathy, balloon tamponade of the uterus. Conclusions. 1. Emergency care for massive bleeding in obstetrics is one of the priorities in reducing maternal morbidity and mortality. 2. Intensive therapy of blood loss should be based on modern recommendations and the use of modern drugs. 3. The indications for transfusion of blood components should be clearly applied.

Background. According to the Decree of the Ministry of Health of Ukraine № 275 issued on 11.09.2018, there is a list of measures to ensure surgical safety and patient’s safety. These measures can be divided into those that should be performed 1) before anesthesia; 2) before skin dissection; 3) before the patient leaves the operating room. Perioperative medicine (POM) is a patient-centered and interdisciplinary perioperative care for surgical patients. Objective. To describe the current recommendations for POM. Materials and methods. Review of available guidance documents. Results and discussion. The pathophysiology of postoperative complications (infectious processes, intestinal paralysis, respiratory failure, kidney damage, etc.) includes the following factors: triggers (anxiety, pain, surgical trauma), patient factors (age, comorbid conditions), the consequences of general operative stress (autonomous system imbalance, inflammation, coagulopathy, metabolic imbalance). Clinical evaluation or biomarkers should be used to identify high-risk patients in the perioperative period. Measures to improve postoperative rehabilitation should be carried out in the pre-, intra- and postoperative period. Thus, in the preoperative period it is necessary to examine the patient, to provide the carbohydrate load 2 hours before the intervention, to conduct antibiotic prophylaxis, to correct or stabilize the comorbid diseases (especially cardiovascular and renal diseases, diabetes, anemia). In the intraoperative period it is necessary to maintain normovolemia and normothermia, to use protective mechanical lung ventilation, to limit the use of opioids, to perform extubation immediately after the intervention. In the postoperative period early activation, early enteral nutrition and early removal of drainages and catheters should be used. The key components of POM include the identification of low-risk patients in order to save resources, the identification of high-risk patients with the possible use of alternative management strategies, and the frequent risk reassessment. The main components of the success of anesthesia include preoperative assessment of the patient’s somatic status and risk, use of controlled hypnotics and effective and predictable muscle relaxant, use of analgesics that break down quickly and have no ability to accumulate, control of the hemodynamics stability, blood gases and acid-base balance. To prevent the perioperative myocardial ischemia, it is advisable to use esmolol – a cardioselective β-blocker of ultrashort action. Preoperative anxiety, intubation and extubation, surgical manipulations lead to the excessive adrenergic response, which justifies the use of β-blockers. The pharmacological effects of esmolol (Biblok, “Yuria-Pharm”) include the reduction of myocardial oxygen consumption, increase of the diastole duration, limitation of the free radicals’ production, control of the activity of metalloproteinases, and the reduction of inflammation around atherosclerotic plaques. In addition, esmolol (Biblok) is able to reduce intra- and postoperative use of opioids, and therefore its use as a component of multimodal total intravenous anesthesia has been proposed. Preoperative administration of esmolol may also be an effective and safe method of myocardial protection in patients undergoing cardiac surgery. β-blockers are well tolerated in patients with acute hypovolaemia during anesthesia, however, episodes of hypercapnia should be avoided during their use. Conclusions. 1. For the optimal POM, the individual risk of perioperative complications should be determined. 2. POM includes a number of pre-, intra- and postoperative measures. 3. The use of ultrashort-acting β-blocker esmolol prevents intraoperative myocardial ischemia, has antioxidant and anti-inflammatory effects, reduces the need for opioids.

Обоснование. Эндотелиальные клетки различных сосудистых зон имеют разные форму и набор рецепторов, что позволяет им быть функционально гетерогенными. Функциями эндотелия являются транспортная, гемостатическая, вазомоторная, рецепторная, секреторная, сосудообразующая и барьерная. Для обеспечения каждой из этих функций эндотелий вырабатывает вещества, отвечающие за диаметрально противоположные функции. Состояние дисбаланса между медиаторами, в норме обеспечивающими оптимальное течение всех эндотелийзависимых процессов, получило название эндотелиальной дисфункции (ЭД). Цель. Охарактеризовать защиту эндотелия и возможности коррекции ЭД в акушерстве. Материалы и методы. Анализ данных литературы по этому вопросу. Результаты и их обсуждение. Оксид азота (NO) играет важнейшую роль в физиологическом функционировании эндотелия во время беременности. Субстратом для синтеза NO выступает L-аргинин. При недостатке NO возникает ЭД, которая в сочетании с дефективной глубокой плацентацией является главной причиной развития основных акушерских осложнений (преэклампсии (ПЭ), синдрома задержки внутриутробного роста плода, преждевременных родов, преждевременной отслойки плаценты, привычного невынашивания). При ПЭ можно отметить изменение эндотелия различных сосудов, в том числе печеночных и мозговых. Выявление ЭД до беременности требует прегравидарной подготовки с помощью донаторов NO (L-аргинина). Накопление в крови беременных метилированных аналогов последнего ведет к снижению биодоступности NO и развитию ЭД. В результате запускается своеобразный порочный круг: ЭД усиливает ишемию и способствует образованию свободных радикалов, которые, в свою очередь, вызывают ЭД. Включение L-аргинина в комплексную фармакологическую профилактику и лечение перечисленных акушерских синдромов с целью преодоления патогенетических эффектов метилированных аналогов L-аргинина, прежде всего асимметричного диметиларгинина (ADMA), является патогенетически оправданным. Успешность данного подхода подтверждена в ряде исследований. Введение большого количества экзогенного L-аргинина вытесняет ADMA и восстанавливает эндогенный синтез NO до физиологического уровня. Тремя основными средствами для устранения ЭД в акушерстве выступают ацетилсалициловая кислота, препараты кальция и L-аргинин (Тивортин, «Юрия-Фарм»). Применение последнего позволяет предотвратить развитие ПЭ у женщин высокого риска, улучшить маточно-плацентарный кровоток, нормализовать объем околоплодных вод. Выводы. 1. ЭД – основное звено патогенеза акушерских осложнений. 2. Основной молекулой, необходимой для нормального функционирования эндотелия, является NO. 3. Тивортин как субстрат для образования NO способствует устранению ЭД и улучшению маточно-плацентарного кровотока.

Background. Pelvic inflammatory diseases (PID) include the wide range of inflammatory processes in the upper reproductive tract of women. 70 % of PID occur in women under 25 years. Adverse consequences of PID include chronization and recurrence of the disease, purulent tuboovarian formations, obstruction of the fallopian tubes, and ectopic pregnancy. Objective. To describe the main aspects of PID treatment and rehabilitation of reproductive health. Materials and methods. Analysis of literature data on this topic. Results and discussion. Risk factors for PID include intrauterine interventions and contraceptives, surgery on uterine appendages, and risky sexual behavior. There are three main targets for PID therapy: infection, release of inflammatory mediators, and repair of damaged tissues. Etiotropic therapy is used to overcome infections, nonsteroidal anti-inflammatory drugs and detoxification drugs are used to prevent active inflammation, and microcirculation correction is used to promote tissue repair. Broad-spectrum antibiotics (ceftriaxone, doxycycline, metronidazole) are used for etiotropic therapy. Fluoroquinolones (levofloxacin) are especially relevant in modern PID treatment regimens because they are effective against 94 % of urogenital tract pathogens, penetrate cell membranes, and slowly cause resistance. The combination of levofloxacin + ornidazole is highly effective against mixed aerobic-anaerobic and protozoal-bacterial infections. A solution for intravenous administration containing a combination of levofloxacin and ornidazole is widely used to treat severe PID. Tobramycin is the drug of choice for PID, mainly caused by antibiotic-resistant intestinal pathogens. After an acute episode of PID, abnormal blood flow in the vessels of the uterus and ovaries is significantly more common. Circulatory disorders contribute to blood stagnation, fibrotization, and sclerosis with the subsequent development of infertility, anovulation, premenstrual syndrome, abnormal uterine bleeding, adhesions, and obstruction of the fallopian tubes. In order to accelerate the excretion of toxic substances and inflammatory metabolites and eliminate oxidative stress, infusion solutions based on sorbitol and L-arginine are prescribed. Sorbitol-based hyperosmolar solution promotes the opening of precapillary sphincters, improves the rheological properties of blood, corrects metabolic acidosis and normalizes water-electrolyte balance. L-arginine solution, in turn, causes dilatation of peripheral vessels, promoting better microcirculation. L-arginine also acts as a substrate for the NO formation. The latter has an antibacterial activity, promotes the migration of T-cells, and takes part in the regulation of the sex hormones synthesis in the ovaries. According to our own data, infusions of L-arginine in PID reduce the proportion of adhesions from 34 to 5.4 %. Conclusions. 1. PID is a spectrum of diseases with a number of adverse consequences, a significant part of which develops in young women. 2. The main components of PID treatment and restoration of reproductive health include elimination of the pathogen, blockade of inflammation and detoxification, correction of microcirculation and tissue repair. 3. Infusion solutions based on sorbitol and L-arginine are successfully used in the comprehensive therapy of PID.

Background. Deep and versatile disorders in case of acute diseases can lead to severe metabolic disorders that are life-threatening and require immediate care. Such conditions include carbohydrate metabolism disorders (CMD): ketoacidosis, non-diabetic ketoacidosis, ketoacidotic and hyperosmolar coma, hypoglycemic syndrome, hypoglycemic and lactic acid coma. Objective. To describe the possibilities of CMD correction. Materials and methods. Analysis of literature sources on this topic; own study involving 126 patients with CMD. Patients were prescribed classic and balanced crystalloids (1200-1400 ml per day), in case of ketoacidosis – Xylate (6-8 ml/kg/day), in case of hyperosmolar conditions – Volutenz (400-600 ml per day). Results and discussion. Necessary laboratory tests in CMD include the assessment of glycemia, potassium, sodium, urea, creatinine, acid-base status, ketonemia, ketonuria; clinical blood test; blood culture and antibiotic sensitivity determination (according to the indications). It should be noted that the level of glycemia in diabetic ketoacidosis (DKA) can vary from a slight increase to a severe hyperglycemia. In case of the clinical picture of advanced ketoacidosis the semiquantitative analysis can reveal 3-4 pluses of ketonuria. However, the nitroprusside method allows to determine acetoacetic acid only, whereas the severe DKA is characterized by the more pronounced increase in the content of β-oxybutyric acid. It may create the preconditions for the underdiagnosis of ketoacidosis. Due to certain features of the analysis, ketosis is usually diagnosed in a decompensated state. Therefore, first of all, it is necessary to be rely by a clinical condition of the patient. Infusion therapy (IT) for DKA involves the use of 0.9 % NaCl solution or Ringer’s solution. If the patient has hypernatremia, 0.45 % NaCl solution is administered. During the first 30-60 minutes of treatment one should administered 1 liter of these solutions. Subsequently, the infusion is continued at a rate of 4-14 ml/kg/h until the glucose level reaches <12 mmol/L, then the infusion should be continued with 5 % glucose solution. IT must be performed with caution in elderly patients and people with heart failure. In addition to IT, insulin therapy (0.1 U/kg/h) is prescribed for DKA, followed by dose adjustment to ensure a decrease in blood glucose concentration at a rate of 2-3 mmol/L. Acidosis is corrected by IT and insulin therapy. Treatment of severe acidosis (pH <7.0) with bicarbonate requires dose adjustment under acid-base control. Xylitol (Xylate, “Yuria-Pharm”) is the main antiketogenic solution. It enters the pentose phosphate metabolism, increases the intensity of glycolysis, enhances glycogen production in the liver and stimulates insulin secretion. On the background of Xylate use, the content of β-oxybutyrate in the urine is halved in 5 hours, and the level of acetone – decreases in 2.5 times in 2 hours. Xylate reduces lactate levels and normalizes tissue perfusion. The unique effects of Xylate include pronounced antiketogenic effect, correction of metabolic acidosis, role as a non-insulin-independent energy source, correction of water-electrolyte balance, and hydration. Evaluation of the effectiveness of therapy in patients with DKA should include regular monitoring of neurological status. If deterioration is observed, cerebral edema, stroke, infectious diseases of the central nervous system, traumatic brain injury, hyperosmolar condition should be excluded. In the latter case, it is advisable to enter a hypotonic solution of 0.45 % NaCl. Because the use of such solutions is associated with a risk of cerebral edema, most recommendations prefer isotonic solutions. In the own study, the described above IT scheme helped to reduce the total volume of infusions, increase diuresis, improve consciousness on the 3rd day of treatment, and reduce the length of stay in the intensive care unit. Conclusions. 1. Many patients develop CMD, which worsen the course and prognosis of the underlying disease. 2. The use of IT should be started at the first signs of DKA. 3. Modern antiketogenic agent Xylate affects the pathogenesis of CMD and has an additional energy effect.

Background. In case of coronavirus pneumonia, the virus damages the cells of bronchi and alveoli, as well as triggers a powerful inflammatory response that disrupts the surfactant and prevents the adequate oxygenation. These pathogenetic links lead to the development of acute respiratory distress syndrome, multiorgan hypoxia and disseminated intravascular coagulation syndrome. Objective. To find out the main pathogenetic links that can be affected by coronavirus disease (COVID-19) treatment. Materials and methods. Analysis of literature sources on this topic. Results and discussion. Hypoxia is one of the main backgrounds of coronavirus organ damage in COVID-19. The consequences of hypoxia include the imbalance between aerobic and anaerobic glycolysis, increased lipid peroxidation, acidosis, microcirculation disorders, edema. Pathologically active inflammation is another background. It leads to the damage of pulmonary capillaries, microcirculation disorders and the development of acute respiratory distress syndrome with increased hypoxia. Since the reactive oxygen species are the main inducers of apoptosis and mitochondrial dysfunction, it is necessary to prescribe antioxidant therapy. Edaravone (Ksavron, “Yuria-Pharm”) quickly neutralizes lots of free radicals, inhibits lipid peroxidation and activates the own antioxidant defense. Other components of the pathogenetic therapy of COVID-19 may include Tivortin and Tivorel (“Yuria-Pharm”). L-arginine (Tivortin) is a nitric oxide donor. Its administration has vasodilating, immunostimulating, membrane stabilizing, cytoprotective and antioxidant effects. Tivorel also contains L-carnitine, which inhibits apoptosis, has antioxidant and cardioprotective effects. In case of pneumonia, it is advisable to use Reosorbilact (“Yuria-Pharm”), which prevents pulmonary edema and restores microcirculation. Conclusions. 1. Hypoxia and hyperinflammation are the main elements of the COVID-19 pathogenesis. 2. Edaravone (Ksavron) neutralizes free radicals and activates own antioxidant defense. 3. L-arginine (a component of Tivortin and Tivorel) has vasodilating, immunostimulating, membrane stabilizing, cytoprotective and antioxidant effects. 4. Reosorbilact prevents pulmonary edema and restores microcirculation.

Background. The goals of infusion therapy (IT) include the restoration of adequate tissue perfusion, maintaining the quantity and quality of the body fluid sectors, correction of homeostasis parameters. In addition, IT can be used for parenteral nutrition, reducing the risk of thrombosis and urinary tract infections. Objective. To identify key IT parameters of a cancer patient. Materials and methods. Analysis of the available literature on this topic. Results and discussion. Indications for IT include hypovolemia, cellular and protein deficiency of blood, nutrition disorders, intoxication, disorders of hemostasis, hemorheological properties, fluid and electrolyte balance, acid-base status. Cancer patients often have the listed syndromes. The appropriate infusion volume should not be exceeded, as the hypervolemia is accompanied by edema, multiorgan dysfunction and worsening of the prognosis. On the other hand, dehydration is the most common fluid and electrolyte balance disorder in the elderly. It is an independent predictor of mortality and high healthcare costs. At any IT administration it is necessary to assess the volemia condition, to determine the cause of the deficiency, to choose the optimal solution and infusion rate, to set and to monitor target values. Capillary filling time, heart rate, blood pressure, jugular veins’ condition, skin turgor, pulmonary and cardiac auscultation data, edema control, diuresis rate, and weight changes are used to assess volemia. Peculiarities of the elderly and debilitated patients, which should be taken into account when prescribing IT, include the loss of thirst feeling, deterioration of renal function and worsening of hormonal regulation of fluid and electrolyte balance. Anticancer therapy has a number of side effects, and some of them can be eliminated with the help of IT. The amount of fluid required should be calculated based on physiological needs (30-40 ml/kg/day), deficiency severity and pathological losses (fever, blood loss, polyuria, perspiration, drainage losses). Plasma replacement solutions can be divided into crystalloids (iso- and hypertonic saline, Ringera lactate) and colloids (albumin, solutions of gelatin, dextranes, hydroxyethyl starch). Crystalloids are recommended for short-term interventions, while long-term therapy requires colloids or balanced solutions, as the introduction of unbalanced solutions is accompanied by such risks as hyperchloremia, dilutive acidosis, acute kidney damage, and systemic vasoconstriction. In settings of the chronic inflammation, which often accompanies oncological diseases, the role of thirst as a means of controlling osmolarity changes. Hyperosmolarity may also accompany central diabetes mellitus and tumor metastases to the hypothalamus. Hyperosmolarity leads to the microcirculatory disorders, increased inflammation, cachexia development and multiple organ failure. Another feature of IT in oncology settings is the disruption of tissue energy supply due to nutritional deficiencies and changes in metabolism. Xylitol (Xylate, “Yuria-Pharm”) can be used to eliminate this problem. Xylitol is a five-atom alcohol, which is directly included into the pentose phosphate cycle. The benefits of xylitol include metabolism stabilization in people with diabetes, promotion of slow but stable energy production, antiketogenic properties, improved metabolism of B vitamins, cholekinetic action, and high safety. Xylitol is not used by the tumor cells as an energy substrate. The role of xylitol (Xylate) in IT is to increase the volume of circulating plasma, to reduce the interstitial edema, to decrease the production of ketone bodies, to activate the antioxidant systems, and to increase alkaline blood reserve. It has been reported that xylitol infusion has an oncosuppressive effect due to its antioxidant effect and inhibition of glucose utilization by tumor cells. Conclusions. 1. IT is an important component of cancer treatment; it should be based on the individual features of the patient. 2. Rational IT eliminates chronic inflammation, endothelial dysfunction and microcirculatory disorders. 3. Rational IT is based on the correct choice of solution, its timely introduction and frequent evaluation of the infusion response. 4. Xylate (“Yuria-Pharm”) has a multifunctional effect in oncology: eliminates dehydration, corrects energy deficiency, and has a direct oncosuppressive effect.

Background. Elimination of intoxication syndrome is one of the main components of sepsis treatment. The Rheo-STAT study is an interventional open multicenter randomized controlled trial of the efficacy of Reosorbilact (“Yuria-Pharm”) in the treatment of intoxication syndrome. The study was conducted in 7 countries, patients of the sepsis subgroup were recruited in 5 of them (Ukraine, Moldova, Georgia, Kazakhstan, Uzbekistan). Objective. To determine the efficacy and safety of Reosorbilact in patients with sepsis. Materials and methods. The study involved 628 adult patients with sepsis, peritonitis, pneumonia and burns. The subgroup of sepsis consisted of 180 people (72 % males, mean age – 41.3 years), the most common comorbidities were cardiovascular diseases (24 %), diabetes mellitus (15 %), and infectious diseases (8 %). The inclusion criteria were the following: age 18-60 years, diagnosis of sepsis, established by the ACCP/SCCM criteria ≤24 hours before the initial visit, obtaining of the informed consent, baseline SOFA scale value ≥2. The primary endpoint was the total score on the SOFA scale on the 3rd day of treatment compared to the baseline value. The secondary endpoints included the change in the overall score according to the APACHE II, SAPS II, MODS, PSI/PORT, CURB-65 scales; changes in biochemical, immunological and integral markers of endogenous intoxication. Results and discussion. Low-volume infusion therapy with Reosorbilact (200-400 ml per day) resulted in an increase in circulating blood volume and a decrease in the total volume of infusions required without the risk of volume overload, which is especially important for critically ill patients. Exogenous lactate in Reosorbilact did not increase the content of endogenous lactate (1st day – 2.27 mmol/L, 3rd day – 1.63 mmol/L), which indicates the high safety of the solution. In the complex of intensive care administration of Reosorbilact helped to reduce hyperthermia (1st day – 38.2 °C, 3rd day – 36.8 °C, p<0.001), heart rate (1st day – 95.43 beats/min, 3rd day – 81.13 beats/min, p<0.001) and the number of leukocytes (1st day – 14.5×109/L, 3rd day – 8.8×109/L) as a marker of endogenous intoxication. During 3 days of therapy Reosorbilact also normalized the acid-base composition of the blood. Conclusions. 1. Elimination of intoxication syndrome is one of the main components of sepsis treatment. 2. Reosorbilact infusion therapy increases the volume of circulating blood without the risk of volume overload. 3. The inclusion of Reosorbilact in the complex treatment of sepsis after 3 days provides a decrease in body temperature, heart rate, white blood cell count and normalization of the acid-base composition of the blood.

Background. Colposcopy in a pregnant woman is carried out to rule out the presence of invasive cervical cancer and to determine the need for targeted biopsy. Indications for colposcopy include pathological cytological smear, abnormal appearance of cervix, or bleeding of unknown origin. Objective. To describe the features of colposcopic examination in pregnant women. Materials and methods. Analysis of own experience and literature sources on this topic. Results and discussion. Literature data indicate the reliability and safety of colposcopic examination of pregnant women. It should be noted that the examination of pregnant women requires a higher qualification from the colposcopist than the examination of non-pregnant women, although the assessment is based on the same principles. Simple colposcopy allows to assess the vascular pattern and color of the epithelium. For a more thorough assessment acetic acid and aqueous Lugol solution probes are carried out. The tasks of colposcopy are to identify the causes of deviations from the norm of cytological examination, to determine the location and boundaries of the pathological area, to choose the location of the targeted biopsy, to carry out medical manipulations within healthy tissues, and to monitor treatment results. To improve the planning of the necessary treatment options for excisions, a Nomenclature of colposcopic terms for cervix was created. Features of the cervix in pregnant women include the increased cervix vascularization, edema and hypertrophy of the papillae of the cervical canal, increased secretory activity of the cervical canal, eversion of the cervical mucosa, dehiscence of the cervical canal, increased metaplasia, deciduosis, prolapse of the vaginal walls. These physiological changes may cause overdiagnosis of pathological conditions. Thus, hypervascularization can mimic atypical vessels, and deciduosis – malignant tumors. Conversely, hypervascularization and bleeding, increased mucus production and prolapse of the vaginal walls can mask the manifestations of the disease, being the causes of underdiagnosis. The progression of eversion during pregnancy allows to visualize the lesion, which was previously localized in the cervical canal, better and better. Deciduosis in pregnant women is divided into decidual ectopia and decidual polyps of the cervical canal. The tumor-like form of deciduosis visually and colposcopically mimics exophytic tumors. The ulcer form is characterized by dense whitening when applying acetic acid, but is not stained with Lugol solution. Manifestations of the papillary form become the most pronounced after the acetic acid test. The vesicular form is the most common and most easily diagnosed by colposcopists. Decidual polyps become densely whitened during the acetic acid test, but unlike cervical cancer, blood vessels do not disappear. These polyps are not stained with iodine. Decidual polyps are usually localized in the areas of the original epithelium; they are multifocal and small in size. Instead, malignant tumors are localized within the atypical zone of transformation; they are single and have a bumpy uneven surface. Polymorphism and variety of lesions, young age, pregnancy, normal results of cytological examination are more typical for deciduosis. If the colposcopist is unsure of the benign nature of the process, a targeted biopsy should always be performed. Conclusions. 1. The purpose of colposcopy in a pregnant woman is to rule out the presence of invasive cervical cancer and to determine the need for targeted biopsy. 2. Indications for colposcopy include pathological cytological smear, abnormal cervix appearance, or bleeding of unknown origin. 3. Physiological changes during pregnancy can be the cause of hyper- and hypodiagnosis of pathological conditions. 4. If the colposcopist is unsure of the benign nature of the process, a targeted biopsy should always be performed.

Background. A doctor often has to answer the question whether it is sufficient to treat tuberculosis (TB) exclusively with the oral forms of anti-tuberculosis drugs (ATD). In general, the answer is yes, if the absorption of drugs and their delivery to the affected organs is not impaired. However, drug absorption is often impaired due to hypoalbuminemia, TB of the gastrointestinal tract or central nervous system, concomitant diseases of the digestive system, alcoholism, hyperthyroidism, diabetes, or in the elderly patients. Objective. To evaluate the feasibility of using infusion forms of ATD. Materials and methods. Review of current guidelines. Results and discussion. The advantages of exclusively oral administration of ATD include convenience, low cost, the possibility of usage in an outpatient setting, whereas the main disadvantage is that it is not always possible to create the required concentration of ATD in blood plasma. In turn, the advantages of intravenous ATD include the creation of maximal concentrations in blood plasma and foci of infection, fewer side effects in the digestive system, patients’ awareness of the importance of treatment, whereas disadvantages are high cost and low adherence to treatment. The use of part of the ATD as a step therapy (course of intravenous infusions with subsequent transition to oral administration) allows to create the maximal concentration of active substances in blood plasma and affected organs at the beginning of treatment, to provide better cost/effectiveness ratio in comparison to previously listed regimens, and to increase the treatment adherence without compromising the quality of life of patients. The additional cost of intravenous ATD delivery devices is the main disadvantage. Criteria for the transition from the infusions to oral administration are the elimination of bacterial excretion, obtaining a stable positive dynamics of the clinical condition, elimination of the causes of the need for intravenous treatment (normalization of swallowing function, elimination of malabsorption). Indications for step therapy include the severe forms of TB, severe disorders of the central nervous system and gastrointestinal tract, the presence of severe comorbidities, pre- and postoperative periods, mental disorders, side effects of 3rd-4th degree in case of oral ATD intake. The duration of the infusion course is determined individually, but in average it is about 1-2 months. Such drugs as rifampicin, isoniazid, ethambutol, levofloxacin, moxifloxacin, linezolid, and carbapenems exist in the infusion form. Conclusions. 1. Infusion of ATD as a part of step therapy can improve the quality of treatment of TB patients. 2. Criteria for the transition from infusions to oral administration are the elimination of bacterial excretion, obtaining a stable positive dynamics of the clinical condition, elimination of the causes of the need for intravenous treatment. 3. The duration of the infusion course is determined individually (in average – 1-2 months).

Background. Tuberculosis (TB) of the central nervous system (CNS) is the most severe and life-threatening form of TB. Diagnosis of TB of CNS is difficult, and treatment is suboptimal. At present, the treatment of tuberculous meningitis (TBM) involves the same drugs and doses as for pulmonary TB, however, the problem is that not all the drugs cross the blood-brain barrier. Objective. To describe the penetration of anti-TB drugs (ATBD) into the foci of infection in patients with TB of CNS and the choice of pharmacotherapy. Materials and methods. Analysis of literature sources on this issue. Results and discussion. Options for optimizing the TBM treatment include a non-pharmacological approach, treatment prolongation, and increasing the residence time of ATBD at the infection site. A meta-analysis of 17 observational studies found no significant benefits of 9-month treatment over 6-month regimens. To increase the residence time of the drug in CNS, you can increase the dose of drugs that poorly penetrate the CNS, add drugs with better brain penetration characteristics, modify drug delivery systems and physical and chemical properties of drugs. The optimal dose provides the maximum effectiveness of the active substance on the background of the minimum number of side effects, so increase of the dose without taking into account the risks of side effects is not advisable. One of the main ATBD rifampicin is characterized by poor penetration into the cerebrospinal fluid. The killer activity of rifampicin depends on its concentration. In our own study, it was found that the administration of a high dose of rifampicin (600 mg) intravenously for 14 days was characterized by lower mortality in patients with TBM than treatment with oral rifampicin (standardized risk ratio was 0.42). Intravenous high-dose treatment was safe and well tolerated by patients. The disadvantages of this treatment include its high cost, invasiveness and poor availability. A meta-analysis of Indonesian patient data confirmed that high doses of rifampicin were associated with lower mortality (Svensson E. et al., 2019). Other drugs that need research in TBM include a new drug bedaquiline, fluoroquinolones (levofloxacin), linezolid. Isoniazid, pyrazinamide, cycloserine, ethionamide, prothionamide are also characterized by the good permeability to cerebrospinal fluid. Therefore, in a strategy to optimize the TBM treatment high-dose rifampicin, high-dose isoniazid and pyrazinamide (?) are the first line, and cycloserine, ethionamide, linezolid, delamanide, pretomanide – the second line. Conclusions. 1. Diagnosis of TB of CNS is difficult, and treatment is suboptimal. 2. Not all the drugs cross the blood-brain barrier. 3. Options for optimization of the TBM treatment include a non-pharmacological approach, prolongation of therapy and increasing the residence time of ATBD in the infection focus. 4. Administration of high-dose rifampicin (600 mg) intravenously for 14 days was characterized by lower mortality in patients with TBM than treatment with oral rifampicin. 5. High-dose rifampicin, high-dose isoniazid and pyrazinamide (?) are the first line of TBM treatment.

Stem cells have attracted scientific, clinical and public interest because they can regenerate and develop in certain types of cells, depending on their source of origin and biological plasticity. Several strategies for the use of cell therapy are currently being explored. A total of 8357 clinical trials of various stages using stem cells have been registered. The possibility of using multipotent mesenchymal stromal cells in patients with COVID-19-induced complications is being actively investigated. However, among the stem cell products, the U.S. Food and Drug Administration (FDA) has so far approved only those that are produced from umbilical cord blood. In the USA and European countries, there are private clinics that provide services for the collection and cultivation of stem cells, mainly autologous. Such medical centers can become the point of concentration of personalized medicine, focused on the needs of a particular patient and his/her possibilities of receiving targeted therapy for severe, difficult-to-treat conditions using modern methods in cellular technologies. The article presents an analysis of existing strategies for the therapeutic use of stem cells and the most promising directions for their further study.

BACKGROUND. To date, radiological criteria for the diagnosis of viral pneumonia associated with SARS-CoV-2 have been established, and treatment regimens for patients depending on the severity of coronavirus disease (COVID-19) have been developed for both outpatient and inpatient settings. Many patients, regardless of the form and severity of the coronavirus infection, suffer from a range of symptoms for weeks or even months that reduce their quality of life. Therefore, the diagnostics of complicated course of community-acquired pneumonia of viral etiology (COVID-19) via using computed tomography (CT) of the chest becomes relevant. OBJECT. To diagnose a complicated course of community-acquired pneumonia of viral etiology (COVID-19) according to CT of the chest. MATERIALS AND METHODS. A group of patients referred for treatment to the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the NAMS of Ukraine with complications of pneumonia from other medical institutions where they were treated for community-acquired pneumonia of viral etiology (COVID-19) 2-3 months ago. Chest CT of 20 patients (12 men and 8 women aged from 24 to 66 years) were analyzed. All patients complained of shortness of breath, cough, lack of significant improvement in general condition after discharge from the hospital. RESULTS AND DISCUSSION. Typical complications of community-acquired pneumonia of viral etiology (COVID-19) were determined by CT: 10 % of patients showed gradual progression of viral pneumonia (numerous opacities were identified as “ground glass”, consolidation and the “crazy paving” symptom); 15 % – signs of thrombosis of the pulmonary arteries branches; 25 % – exacerbation of chronic obstructive pulmonary disease with preservation of signs of bilateral polysegmental viral pneumonia; 20 % – exacerbation of asthma with signs of bilateral polysegmental viral pneumonia in the regression phase; 30 % – bullous pulmonary emphysema (“vanishing lung syndrome”). CONCLUSIONS. Typical complications of pneumonia of viral etiology (COVID-19) indicate that the inflammatory process does not end after inpatient treatment and the presence of a negative PCR test, and patients need further careful monitoring and correction of treatment. CT is an objective and most informative diagnostic method of complicated community-acquired pneumonia of viral etiology (COVID-19).

BACKGROUND. The era of coronavirus disease (COVID-19) set the such task for lung ultrasound (LUS): to identify the presence of COVID-pneumonia, its differential diagnosis with other conditions which characterized by interstitial edema, determining the severity of lung damage and its location, the dynamics of pulmonary changes tissue, the development of complications, as well as to assess the effectiveness of personalized therapy. OBJECTIVE. To develop a national LUS protocol for COVID-19 based on a balance of completeness of information with the optimal minimum of time and effort for medical staff, who often do not specialize in ultrasound using, with ultrasound equipment of basic and middle classes. MATERIALS AND METHODS. A total of 1576 patients with COVID-19 were examined. There were 810 women (51.4 %) and 766 men (48.6 %). The age of the examined patients was in the range of 18-83 years, the average age was 52.3±14.6 years. 4710 LUS were performed, of which 1572 were repeated and 3144 – in the dynamics. Polysystemic ultrasound was performed in 275 patients. Ultrasound devices of both domestic and foreign production were used: Soneus P7 (Ultrasine, Ukraine), HandyUsound (Ukraine), Xario, USAP-770A (Toshiba, Japan), GE Venue (General Electric, USA) and TE7 COVID (Mindray, China) with ultrasound probes of convex, linear and microconvex formats. RESULTS. Summarizing our own experience with patients with COVID-19 in 2020-2021, we have developed a version of the LUS-protocol, which has a convenient form of recording all stages of ultrasound with maximum coverage of the entire volume of both lungs according to a clear algorithm, a graphical form, clear ultrasound semiotics and diagnostic scoring criteria for the severity of lung damage. CONCLUSIONS. 1. Clinical data indicate the feasibility and effectiveness of using LUS for dynamic monitoring of patients with pneumonia caused by SARS-CoV-2, especially in oxygen-dependent patients at their bedside (POCUS principle). 2. Optimization of the use of radiological diagnostic methods due to ultrasound makes it possible to reduce the radiation dose of the patient.3. The use of LUS allows more adequate decision-making on the need for intensive and interventional therapy, leads to faster diagnosis, improved medical care, reduced length of stay of patients in ICU, as well as reducing the total cost of treatment.4. Ability to reduce the impact of SARS-CoV-2 on healthcare professionals by limiting physical contact with the patient. 5. The standardized Ukrainian protocol of LUS provides availability, efficiency and clear interpretation of the received data at its use by different doctors in different medical institutions. The integration of the protocol in to the ultrasound machine provides optimization of the workflow process.

Objective. To study the energy effect of infusions of the drug Sorbilact in the body of operated patients with cancer of the middle thoracic esophagus. Materials and methods. Clinical use of the drug Sorbilact was performed in 30 operated patients with cancer of the middle thoracic esophagus (the main group). Sorbilact was administered intravenously immediately after surgery, drip at a rate of 30 drops per minute for 5 days at a dose of 800 ml per day. Plasma urea concentration was determined before infusions on the 1st day after surgery, and on days 2, 3, 5 after Sorbilact infusions. The control group – 25 operated patients – was administered 5 % glucose solution at a dose of 800.0 ml. Results and discussion. In the first days after surgery in patients with cancer of the middle thoracic esophagus an increase in the concentration of urea in blood plasma was revealed. In the main group of operated patients after resection of the middle thoracic esophagus in repeated studies on the 2nd, 3rd, 5th day after infusions a significant decrease in the concentration of urea in blood plasma was showed. It indicates that less endogenous protein is consumed for energy purposes, and the caloric needs of the operated body are covered by intensive absorption of Sorbilact, which reduces the catabolism of internal proteins, resulting in reduced nitrogen production, which is manifested in a decrease in the concentration of urea in blood plasma and its difference. In the control group of operated patients in repeated studies on the 2nd, 3rd, 5th day after infusions an increase in plasma urea was revealed, which indicates insufficient caloric energy expenditure of the operated organism. Conclusions. Intravenous infusions of the drug Sorbilact according to the indicator of increment of urea in blood plasma in operated patients after resection of the middle thoracic esophagus in the early postoperative period show a pronounced energy effect.

Objective. To analyze the presence of concomitant pathology in patients of different age categories who underwent hip arthroplasty by different methods. Materials and methods. The study retrospectively analyzed 555 case histories of patients (282 men and 273 women) for the presence of concomitant pathology in different age groups (from 20 to 95 years). The age category was determined according to the 2015 World Health Organization age classification. Statistical processing was performed according to StatPlus programs, the differences were considered significant at p

Objective. To study the aggregation activity of platelets in patients with renal hypertension. Materials and methods. The research work was carried out on the basis of the nephrological department of the State Institution NMC RT “Shifobakhsh”. The study included 46 patients aged 25 to 60 years with chronic pyelo- and glomerulonephritis. The patients were divided into two equal groups: first, the control group received standard therapy in accordance with the clinical protocol of the Tajik Association of Nephrologists; second, the main group, along with complex pathogenetic therapy in order to stabilize the hemostasis system and improve endothelial dysfunction, used the drugs Tivortin (intravenously drip and then long-term per os Tivortin aspartate) and Rheosorbilact intravenously drip. In addition to the generally accepted studies of patients with kidney pathology, emphasis was placed on the criteria for platelet quality (number, mean platelet volume, platelet distribution index, thrombocyte and large erythrocyte ratio) and studies of the hemostasis system (fibrinogen, prothrombin time, activated partial thromboplastin time, prothrombin relation). Results. There were found the hemostasis in microvessels, increases of the blood viscosity, the activation of systemic thrombus formation, and the progression of endothelial dysfunction in patients with renal hypertension. The results of observation of the dynamics of platelet aggregation activity under the influence of the combination of the studied drugs in this category of patients prove an effective decrease in its level. It is also necessary to emphasize the antiplatelet effect of this combination in relation to the prevention of microthrombosis and the pronounced endothelioprotective effect in patients with renal pathology. Conclusions. The complex therapy of patients with renal hypertension with Tivortin and Rheosorbilact is an effective way to stabilize hemovascular hemostasis. The effects of this therapy contributed to the improvement of the clinical condition of the patients, and during repeated examinations, there was a stable preservation of the decrease in the level of platelet aggregation activity.

Background. High incidence and lethality of infectious disease is an actual problem of the 21st century medicine. Infectious diseases are one of the most common causes of morbidity worldwide. Untreatable bacterial infections with the current available antibiotics lead to increased morbidity and mortality. Antimicrobials are the most commonly prescribed drugs in the community and hospital setting. However, inappropriate use of antibiotics in recent years has particularly increased the number of antibiotic-resistant strains. Antimicrobial resistance is a significant global health threat. Without effective antimicrobials, much of the progress made in fighting infectious disease would be lost. The recent rise in resistance to these critical medicines is therefore extremely worrisome. Objective. To study epidemiological and clinical aspects of antibiotics using in Georgia. Materials and methods. The study was retrospective-prospective. We used ATC/DDD methodology for epidemiological research of antibiotic using in the country and it held 2011-2019. According to this methodology, we calculate defined daily doses of antibiotics per 1000 inhibitors (DID). The point prevalence survey was performed in 2017-2019 in Georgian hospitals for clinical research. Results and discussion. In last year increased antibiotic using in Georgian population. The lowest rate was in 2014 (19 DID) and the highest in 2019 (37 DID). The most commonly used antibiotics in Georgia are ceftriaxone, amoxicillin / clavulanic acid, azithromycin and ciprofloxacin. Frequency of antibiotic treatment in Georgian hospitals ranges between 77.6 % (2017) and 86.1 % (2019). The use of third generation cephalosporin ranges between 61.9 % (2017) and 59.6 % (2019). From the clinical aspects of antibiotic therapy, it is noteworthy that prevalence of antibiotic using in Georgian clinics is high and ranged from 77.6 % (2017) to 86.1 % (2019). Antibacterial prophylactic decreased and ranged from 38.3 % (2017) to 20.3 % (2019). Antibiotic selection according to guidelines on the most frequent nosology ranges between 73.8 % (2017) and 69.2 % (2019). Empirical antibiotic therapy decreased in last years and ranges between 92.2 % (2017) and 69.2 % (2019). Conclusions. Increasing rate of antibiotic using in Georgian population and high use of broad-spectrum antibiotics in remarkable. In hospitals, antibiotics are prescribing according to the national or intra hospital guidelines, but there prevalence rate is high. Patient histories included information about general criteria of starting antibiotic therapy. Stop or review date of antibiotic treatment after 72 h in poorly presented. We think that it is very important to continue epidemiological and clinical research for future. Also update or developed new guidelines will be perfect way for optimization.

Objective. To analyze the effectivity of the use of antiviral drugs Sovaldi 400 mg and Harvoni 90/400 mg in hematological patients. Materials and methods. Under our supervision there were 68 patients: 43 (63 %) male and 25 (37 %) female, age from 23 to 80 years, who were treated with antiviral medications intended to hepatitis C virus (HCV). The drugs had prescribed depending on the genotype of the virus; the degree of liver damage; factors that aggravate the course of the disease and the treatment process; responses and adverse reactions that may occur during the process of taking the drug and the timing of use. The 26 patients with genotypes 1 (3), 1c (4), 2 (4), 3a (14) and 1 patient with atypical genotype Sovaldi 400 mg received. Harvoni 90/400 mg was used for treatment HCV 1b genotype in 41 patients and in 1 patient with an atypical genotype. To all patients were investigation according to the algorithm for the diagnosis and treatment of HCV: general clinical (biochemical and hematological) studies and examinations to determine the genotype of the virus, viral load, the degree of liver fibrosis. Results and discussion. Given the high infection rate of hematological patients with HCV, which does not allow full treatment, including surgery and chemotherapy, under the program “Treatment of patients with viral hepatitis” antiviral drugs were purchased and treatment was performed in groups of hematological patients. In particular, in patients with the following diagnoses: non-Hodgkin lymphoma (5); myelodysplastic syndromes (1); Hodgkin lymphoma (1); haemophilia A (13) and B (3); leukopenia (3); disaggregation thrombocytopathy (16); immune thrombocytopenic purpura (13); secondary erythrocytosis (5); iron deficiency anemia (5); polycythemia vera (2); chronic lymphocytic leukemia (1). Antiviral therapy was performed according to the clinical protocol for the treatment of viral hepatitis B and C in hematological patients under the supervision of an infectious disease specialist and hematologist. Most patients tolerated treatment satisfactorily and without complications. Conclusions. In the last years, direct-acting antiviral drugs become the standard of treatment in hematological patients. For today, HCV should not hinder on the basic of full treatment in the hematological patients as most infected patients may receive antiviral therapy.

Objective. To investigate the morphological features of the internal organs of experimental animals and identify potential target organs with the introduction of ultra-high doses of the drug ALX-5 % and the drug with double the concentration of components ALX-2N. Materials and methods. The experiments were performed on outbred white male mice and outbred white male rats. Animals were administered ALX-5 % and ALX-2N solution. ALX-5 % protein-saline solution contains: donor albumin (5 %) pentatomic alcohol xylitol (5 %), alkalizing components – sodium lactate (1.9 %) and sodium bicarbonate (0.01 %), as well as sodium chloride (0.8 %), potassium chloride (0.03 %), calcium chloride (0.01 %). Theoretical osmolarity – 990 mOsm/l, pH – 6.2-7.4. The drug with double the concentration of ALX-2N contains all these components in double the concentration (osmolarity of the solution – 1980 mOsm/l). ALX-5 % was administered intraperitoneally multiple times at a dose of 174 ml/kg for mice and 90 ml/kg for rats. These doses are conditionally toxic, as these doses are the maximum that animals have been able to administer. Further increase in the volume of infusion solution was not allowed due to possible excessive hypervolemic effect. The ALX-2N solution was administered at a dose of 50 ml/kg. At the end of the experiment, histological preparations were prepared from the internal organs of animals, which were stained with hematoxylin and eosin and toluidine blue and studied under a light microscope. Results and discussion. It was found that when white mice and white rats were injected with the native protein-salt preparation ALX-5 % (osmolarity of the solution – 990 mOsm/l) in ultra-high doses (174 ml/kg for mice and 90 ml/kg for rats) the main target organs were the brain and lungs. Changes in other organs (kidneys, liver, pancreas, spleen, heart) are uncritical. With the introduction of concentrated drug ALX-2N (osmolarity of the solution – 1980 mOsm/l) at a dose of 50 ml/kg in addition to pronounced changes in the lungs and brain, dystrophic changes of heart and liver cells are observed. In all the study groups of animals accumulation of glycogen was observed, which is obviously due to administration of the high dose polyhydric alcohols xylitol and sodium lactate, a significant part of which is metabolized in the liver. Conclusions. According to the results of a comprehensive study of pharmaco-toxicological properties, it was found that the multicomponent protein-salt solution ALX-5 % may be suitable for further clinical study.

Objective. Reducing maternal mortality during massive obstetric bleeding (MOB) through optimizing total hysterectomy technique and improving the quality of infusion therapy. Materials and methods. The analysis and evaluation of the results of MOB treatment in a comparative aspect were carried out in retrospective and prospective groups from 2014 to 2019 in Urgench perinatal center and three maternity complexes of Khorezm region, Uzbekistan. The retrospective group included 72 pregnant women with an average blood loss of 2450.0±80.0 ml, while the prospective group included 78 pregnant women with an average blood loss of 2530.0±70.0 ml. Results and discussion. 1,419 (6.2 %) cases out of 22,896 deliveries in the retrospective group were accompanied by abnormal blood loss, and the MOB frequency of more than 1500.0 ml was determined in 0.3 % of all deliveries. 5 (62.5 %) of 8 cases of maternal mortality were directly related to MOB. In the retrospective group, a total hysterectomy was performed using traditional method for MOB, with an interoperable blood loss of 860.0±110.0 (p

Objective. To study the effect of Rheosorbilact on the main life support systems in patients with massive blood loss in obstetrics. Materials and methods. The study was carried out in 56 puerperas with massive blood loss during obstetric operations for placenta previa. Surgical intervention was performed under general multicomponent anesthesia with mechanical ventilation. After the end of the operation, the patients were on prolonged mechanical ventilation for 4-6 h until the main life support systems were stabilized. With the purpose of infusion therapy were used Rheosorbilact (13-15 ml/kg), 0.9 % sodium chloride solution (25-30 ml/kg) and blood components. The main life support systems were assessed by non-invasive monitoring of central and peripheral hemodynamics and autonomic nervous system. Results and discussion. Blood loss was 1500-2000 ml, which developed within 20 min from the moment of the start of the operation. Taking into account the pharmacological properties of the drugs used, infusion therapy began with a jet intravenous injection of Rheosorbilact followed by the introduction of 0.9 % sodium chloride. After 30 min from the onset of bleeding and the administration of infusion-transfusion therapy, a significant increase in cardiac output over the initial parameters was noted. At the same time, the epicardial fat volume (EFV) significantly decreased by 4.4 %. 30 min after the end of the infusion-transfusion therapy, a stable hemodynamic profile was noted. 4 h after the end of the infusion therapy, there was an increase in cardiac output and MDP relative to the original value, a decrease in post-load and heart rate, an increase in EFV by 8.1 % (p

Background. Clinical experience has shown that in conditions of severe quarantine, patients with small respiratory syndromes do not have access to early and quality differential diagnosis. It increases the risk of hospitalization, in such cases, to the infectious department. In most cases, tuberculosis (TB) treatment is no different in people with coronavirus disease (COVID-19). Objective. Analyze the outlook for the effects of the interaction between COVID-19 and TB, which remains the leading cause of death from a single infectious disease in the world, and for the reduce the risk of TB infection in a pandemic without losing treatment. Results and discussion. Recently, patients with TB and COVID-19 syntropy, which requires off-label therapy, have to be treated more and more often. This is especially true for patients with diabetes who are at risk for both TB and coronavirus infection. In such cases, which account for approximately 10-15 % of the total, oral therapy (per os) has a high risk of being ineffective. Timely infusion therapy for the synthesis of infectious diseases – TB and COVID-19 – reduces the risk of lethal prognosis. The method of intravenous infusions of anti-TB drugs is the ability to quickly create very high concentrations of drugs in the pulmonary artery, bypassing the liver as the main organ of inactivation and presystemic metabolism. Experience with co-treatment of COVID-19 and TB remains limited. However, suspension of TB treatment in patients with COVID-19 should be exceptional. Prophylactic treatment of TB, treatment of drug-sensitive or resistant TB should be continued continuously to protect the patient’s health, reduce transmission of infection and prevent the development of drug resistance. Therapeutic trials and accumulation of practical experience are underway. However, there are currently no warnings regarding the interaction of drugs used in the treatment of COVID-19 and anti-TB drugs, including the use of infusion therapy in severe conditions. Conclusions. Timely infusion therapy for the synthesis of infectious diseases – TB and COVID-19 – reduces the risk of lethal prognosis.

Objective. Thrombocytopenia is a common complication of chemotherapy, which is characterized by a decrease in platelet count

Background. Minimally invasive surgical techniques for inguinal hernia repair reduce the body’s overall stress response to surgical tissue damage, the risk of complications, the percentage of postoperative acute and chronic pain, recovery time. Objective. To improve short-term (acute inguinal pain in the early postoperative period) and long-term (chronic inguinal pain in the long-term follow-up) results of surgical treatment of patients with acquired inguinal hernia by using the modified (sutureless, without mesh fixation) laparoscopic technique of transabdominal preperitoneal hernioplasty (TAPP) with application of Fast Track Surgery guidelines. Materials and methods. The retrospective clinical study included 124 patients aged 18 to 88 years (mean age – 46±2.1) with primary unilateral inguinal hernias who were operated on the clinical bases of the Department of Surgery and Vascular Surgery of Shupyk National Medical Academy of Postgraduate Education. The observation period was 3 years. Modified TAPP was performed in 78 patients (spinal anesthesia, local anesthesia of trocar wounds, terminal peritoneal anesthesia, preperitoneal infiltration of affected inguinal region dissection by local anesthetics, using of anatomical 3D mesh, sutureless restoration of peritoneal defect by electric welding method) and Lichtenstein technique was performed in 46 patients. The peritoneal defect in the main group after implant placement was restored by spot welding. There was experimental study before proceeding the clinical study. The experimental section of the work included 12 rabbits weighing 1.95-3.75 kg (average weight – 2.30±0.52). Each animal was cut peritoneum in three places on both sides of laparotomy with next reconstruction of the defect on one side by welding, and on the other – by suturing with synthetic suture material. Results and discussion. In biological samples from experimental animals, there was decreasing of number of live mesotheliocytes which did not increase the severity of the inflammatory reaction (p˂0.001). A statistically significant difference was observed in the welded scars with higher intensity of collagen formation than in the ligature scars, which provided greater strength of the tissue connection. There was a reduction in the patient’s length of stay in the hospital in 4.2 times in the group of modified technique. There was a reduction in the period before the ability to perform professional duties in 3.4 times in the group of new surgical method. There was no significant difference in the levels of postoperative complications (p=0.036) and re-operations due to complications (p=0.023). In the group of modified surgical treatment there were significant lower rates in the indicators of pain at rest (p

Objective. To define the role of the cryoprecipitate (CP) and prothrombin complex concentrate (PCC) in the acute obstetric blood loss treatment via the assessment of the water sectors’ state, hemostasis, and frequency and severity of clinical manifestations of the multiple organ dysfunction syndrome (MODS). Materials and methods. 140 women had been examined (over the years 2006-2018), whose child delivery or early postnatal period (fourth stage of labor) had got complicated by an acute severe blood loss with a circulating blood volume deficit of 40 to 60 %. Based on the intensive treatment (IT) characteristics, the patients had been divided into three groups. In the group 1 (post-hoc analysis, n=50), a normal acute blood loss intensive treatment as per the relevant clinical protocols of the Health Ministry of Ukraine had been being provided. In the group 2 (n=44), an acute blood loss intensive treatment as per the abovementioned clinical protocols of the Health Ministry of Ukraine with use of the CP as the first-line drug had been being provided. In the group 3 (n=46), the PCC (Octaplex 20 IU/kg) had been added within the treatment. Thereat, there had been assessed such criteria as follows: RBC count, Hb, Ht, prothrombin index (PI), activated partial thromboplastin time, fibrinogen; the water sectors of the human body had been assessed noninvasively, via the integral impedance method; as well as the clinical signs of the MODS. Results and discussion. The use of the CP as the first-line drug at a dose of 8 to 10 units had enabled to get decreased the total volume of the infusion and transfusion media by 13.7 % (p

Objective. To assess the prospects for scientific development of new classes of bronchodilators for respiratory diseases with obstructive syndrome, taking into account future molecular targets. Materials and methods. The analysis of international English scientific information in the systems of surveys and search on the Internet for the last 5 years is carried out. Results and discussion. Currently, there is an increasing interest in the development of new directions for pharmacological correction of the mechanisms of bronchial obstruction. The proposed international protocols are based on several groups of correctors: short-acting and prolonged-acting β-agonists, anticholinergics, methylxanthines, antileukotriene drugs and their combinations, but their safety limits their use in the age aspect. Therefore, the search for new targets for influencing bronchial tone remains relevant in respiratory pathology. There are nine potential new classes of bronchodilators that are being studied. Selective phosphodiesterase inhibitors (PDE) were already known as roflumilast for the treatment of chronic obstructive pulmonary disease (COPD), but the genetic polymorphism of PDE isoenzymes, their different localization in subcellular microdomains, a complex signaling network and their selectivity for cyclic AMP or GMP all make it difficult to obtain and develop effective pharmacological action. Dual PDE3/PDE4 inhibitors are being developed taking into account that the PDE4 isoenzyme – the main one in most inflammatory cells involved in the pathogenesis of bronchial asthma (BA) and COPD, predominates in the smooth muscles (SM) of the bronchi; its inhibition leads to their relaxation, especially when interacting with stimulation of β2-adrenergic receptors. The double inhibition exposure can undoubtedly contribute to bronchodilator and anti-inflammatory activity. Evaluation of zardaverine, benzafentrin, tolafentrin and pumafentrin was carried out in volunteers, but without introduction into the clinic. Nevertheless, ensifenthrin, as the only dual PDE3/PDE4 inhibitor, has been proposed for the stage of clinical development in the treatment of BA, COPD, and cystic fibrosis, taking into account its high affinity for PDE3 (3440 times more against PDE4), mainly with a bronchodilatory effect, more effective in a synergistic combination with β2-agonists or anticholinergics. Dual inhibitors of PDE4/PDE7: these isozymes are expressed in immune cells through the control of cAMP, their double inhibition reduces bronchial hypersensitivity, production of proinflammatory interleukins in the experiment, which retains interest in a number of compounds – PDE4/PDE7 inhibitors. Dual PDE4/PDE5 inhibitors: especially attractive for their multilevel effect on bronchi, reduction of pulmonary hypertension and inflammation, lung remodeling. Thus, the combination of a PDE5 inhibitor (tadalafil) and PDE4 (roflumilast) improves these parameters in preclinical data, but their clinical development is questionable. Agonists of bitter taste receptors – a group of 25 proteins – in addition to the tongue, are found in the respiratory epithelium and in the SM, where their three subtypes (10, 14 and 31) are highly expressed. The activation effect exceeds the relaxation of β-agonists by 2 times, with a high concentration of Ca2+ and relaxation, the search for agonists of this class against the background of a small amount of clinical data continues. Agonists of the E-prostanoid receptor-4 (PGE2): activation of the PGE2 receptor stimulates cAMP, the synthesis of several compounds of this type can relax the bronchi and in histamine spasm, can be interpreted as its key role, when administered orally, although it has not been tested in humans. Inhibitors of Rh0 kinase: these protein kinases are highly represented in contractile SM, the RhoA/ROCK pathway regulates phosphatases of myosin light chains, two molecules have been proposed for clinical use – fasudil and ripasudil (Japan, China), but they have not yet been used in pulmonology for obstruction. Calcilytics: the G-protein receptor (guanine nucleotide) is associated with extracellular Ca2+, regulates the contraction in asthma and is elevated in sputum, also potential bronchodilators for the strategy. Among the new targets, PPAR-agonists should be named, although they affect lipid and glucose metabolism, are able to relax SM in asthma, their effects are debated. Agonists of the receptor relaxin-1 or -2 (studies of serelaxin) as a dilator and antifibrotic drug have demonstrated the generation of relaxing epithelial factors, but T1/2 only 10-20 min requires continuous infusion of 48 h, their conjugation with fatty acids creates a long-acting relaxin-2 analogue. NO donors can be useful, but the release of NO activates superoxide, induces tolerance, therefore these mechanisms are clarified in the experiment. Pepducins – lipidated peptides, through binding to G-proteins or arrestins, can also offer new strategies for signaling responses (biased agonists). Conclusions. New possibilities for the development of bronchodilators are in the preclinical phase, but they can become an addition to the modern optimal therapy for bronchial obstruction.

Objective. To streamline the tactics of infusion therapy in patients with acute cerebrovascular accident (ACVA) in the prehospital stage. Materials and methods. A retrospective, non-randomized study of 49 patients with ACVA who received emergency medical care in the prehospital phase. Results and discussion. Ensuring adequate brain perfusion in the area of ischemia is the main task of emergency medical care ACVA in the prehospital stage (Zozulya I.S., Volosovets A.O., Zozulya A.I. et al., 2019). Among the drugs that effectively improve blood circulation to the brain in the area of ischemia, an important place is occupied by infusion solutions (Semenenko A.I., Kobeliatskyi Yu.Yu., Kondratskyi B.O. et al., 2016). The choice of the optimal qualitative and quantitative composition of infusion solutions in patients with ACVA is one of the most difficult issues of treatment (Halushko O.A., 2017). Infusion therapy for patients with ACVA in the prehospital stage was used according to the Unified Clinical Protocol of Medical Care “Ischemic stroke (emergency, primary, secondary (specialized) medical care, medical rehabilitation)” (Order of the Ministry of Health of Ukraine from 03.08.2012 № 602) according to the following algorithm: 1) providing venous access by standard venous catheterization procedure with asepsis/antiseptics by intravenous catheter № 18; 2) carrying out infusion therapy by introducing 0,9 % sodium chloride solution at a rate of 100 ml×h-1; 3) the introduction of colloidal solutions in patients with ACVA in the prehospital stage was not carried out. Conclusions. The choice of the optimal qualitative and quantitative composition of infusion solutions in patients with ACVA in the prehospital stage is one of the most difficult issues of emergency care. After providing venous access by catheterization of the peripheral vein with a catheter № 18 infusion therapy is carried out by administering 0,9 % sodium chloride solution at a rate of 100 ml×h-1. The introduction of colloidal solutions in patients with acute cerebral circulatory disorders in the prehospital stage is contraindicated.

Objective. To present the immediate results of the splenectomy and preferable variants of transfusion therapy performance in patients with malignant non-Hodgkin’s lymphoma (MNHL). Materials and methods. 109 splenectomies were performed in patients with MNHL at the Department of General and Hematological Surgery of the institute from 1987 to 2020. The surgery was conducted by upper middle laparotomy under general anesthesia with intubation and, in particular cases, under spinal anesthesia. Results and discussion. The indications for splenectomy in patients with MNHL were as follows: massive splenomegaly, abdominal syndrome, associated hemocytopenia, inefficacy of cytostatic therapy, absence of diagnosis. All patients underwent vaccination against capsular bacteria for prevention of post-splenectomy infection in 10-14 days prior to the surgery. In case of anemia, which has been observed in 55 % of patients, the RBC concentrate was applied. All the patients, who received corticosteroid hormones prior to splenectomy, were administered prednisolone and hydrocortisone in the amount of 3 mg/kg of body mass at similar doses in an hour before the surgery for prevention of adrenal insufficiency during the surgery. The patients, who did not receive those medications, were also intramuscularly administered prednisolone at a dose of 0.5 mg/kg of body mass in an hour before the surgery for the same aim. The patients with PLT value 80.0×109/L) underwent two courses of leukapheresis. The patients with concomitant regional portal hypertension and in case of manipulations close to the pancreatic tail were administered somatostatin drugs in the course of the splenectomy. The splenectomy proved to be effective in 100 (92 %) of patients with MNHL: the great tumor mass was removed, the abdominal syndrome and concomitant hemocytopenia were neutralized, the signs of hypersplenism ceased, the hemolysis ceased, the cytostatic therapy became less necessary or unnecessary, the final diagnosis was established. The most serious postsurgical complications were acute adrenal failure (n=3), postsurgical intra-abdominal hemorrhage (n=2), pancreonecrosis (n=6). The postsurgical lethality was 2.7 %. Conclusions. The splenectomy proved to be effective in 92 % of patients with MNHL. The infusion therapy is individual for each patient and may include transfusion surgeries if indicated. The main objective of the infusion therapy in patients with MNHL is prevention and elimination of intra- and postsurgical complications.

Objective. To evaluate the effectiveness of the “Trio” pharmacotherapy regimen in patients with chronic arterial insufficiency IIb-III. Materials and methods. 45 patients with a confirmed diagnosis of peripheral arterial occlusive disease of the lower extremities and chronic arterial insufficiency IIb-III were included in the study. All patients were randomly divided into two groups. Patients from experimental group received “Trio” pharmacotherapy (multicomponent isoosmolar solution containing petoxifyllin; multicomponent hyperosmolar solution containing sodium lactate; L-arginine hydrochloridum solution). Patients from comparison group received medical therapy with multicomponent hyperosmolar solution containing sodium lactate and L-arginine hydrochloridum solution. Results and discussion. The duration of hospital stay was significantly shorter (p

Objective. To evaluate the effectiveness of comprehensive treatment of patients with postoperative hypothyroidism (PH) and non-alcoholic fatty liver disease (NAFLD). Materials and methods. 40 patients (20 men and 20 women) aged 42±6 years with PH and NAFLD were examined. Patients were divided into two groups: main (n=20) and control (n=20). Prior to the study and after 1 month, the level of total cholesterol (TH), triglycerides (TG), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) was determined. Patients in both groups were prescribed levothyroxine sodium (125-175 μg a day). Additionally, the 1st group of patients received arginine hydrochloride 42 mg/ml according to the scheme 200 ml a day per 15 days, the next 15 days L-arginine aspartate 200 mg/ml 5 ml a day. And the control group received only levothyroxine sodium. Results. The level of TH in 1st group decreased from 7.1±0.8 to 6.7±0.4 mmol/l, and in 2nd – from 7.2±0.7 to 6.97±0.35 mmol/l. In the 1st group TG decreased from 3.9±0.4 to 3.5±0.3 mmol/l, and in the 2nd – from 3.8±0.5 to 3.7±0.1 mmol/l. LDL in 1st group decreased from 5.9±1.4 to 5.5±1.2 mmol/l, in the 2nd – from 5.8±1.3 to 5.7±1.4 mmol/l. The level of ALT in 1st group decreased from 47.5±1.82 to 40.1±1.73 IU/l, the level of AST – from 41.3±1.52 to 39.8±1.33 IU/l, in no changes in AST and ALT levels were observed in the control group. Conclusions. Comprehensive treatment of patients with PH and NAFLD contributed to the improvement of liver transaminases (reduction of AST, ALT), as well as the normalization of the lipid profile (reduction of TC, TG and LDL).

The mechanisms of development and clinical manifestations of diabetic ketoacidosis (DKA) are analyzed in the article, the prospects of the use of xylitol-based infusions in the treatment of DKA are discussed. The authors also presented the infusion therapy program and their own experience with the use of Xylat solution. It has been shown that the use of Xylat can have a positive effect on various parts of the pathological process – from elimination of dehydration to the correction of disorders of acid-base status (ABS). Xylat should be started with the first signs of DKA, even in the absence or low severity of ketonuria according to the nitroprusside test. This tactic makes it possible to normalize ABS more quickly and reduce the overall amount of infusion therapy.

Objective. Investigate directly the clinical efficacy of L-arginine aspartate in the treatment of patients with essential arterial hypertension (EAG) and type 2 diabetes mellitus (DM). Materials and methods. The study included 43 patients with EAG II in combination with type 2 DM. The mean age of patients was 55,7±0,6 years, of which 20 (46,5 %) were men and 23 (53,5 %) were women. The duration of the disease on the EAG averaged 8,4±0,4 years, on type 2 DM – 6,5±0,5 years. A comprehensive clinical, laboratory and instrumental examination was carried out. All patients were divided into two groups. Patients in both groups received ramipril 5-10 mg a day in combination with amlodipine 5-10 mg a day and antidiabetic drugs (metformin, gliclazide or a combination thereof) as basic therapy. Patients in group 2 (n=22) were additionally prescribed the drug L-arginine aspartate orally 3 g 3 times a day for 4 weeks. The course of treatment was repeated after 2 months. Results and discussion. In group 2 there was a more pronounced tendency to decrease the average daily and night blood pressure levels, in particular diastolic (3,2 and 2,9 mm Hg; p>0,05) and heart rate (by 17,3 %; p0,05). Conclusions. L-arginine aspartate should be used in patients with EAG in combination with type 2 DM and microalbuminuria to increase the cardio- and nephroprotective efficacy of basic therapy.

Objective. To study the effects of low-volume infusion therapy on the pathogenetic elimination of endogenous intoxication in a patient with coronary heart disease. Materials and methods. The study included 30 patients diagnosed with COVID-19. The age of the patients was 45-65 years. All patients underwent generally accepted clinical laboratory and instrumental examinations. Rheosorbilact 200 ml intravenous was prescribed to all patients for the purpose of low-volume infusion therapy to reduce metabolic disorders, reduce the amount of free radicals and weaken inflammatory reactions, eliminate endogenous intoxication. The drug contains potassium chloride, calcium contains magnesium chloride, sodium lactate, sodium chloride and sorbitol. Results and discussion. The drug was positively received by patients during treatment and no side effects were observed. A “mild” effect on the pH of the blood was observed during the determination of Rheosorbilact. In addition, lactate has been shown to have a positive effect on cardiac function, liver and kidney detoxification function. The positive effect of Rheosorbilact on the functional state of the endothelial layer of microvascular vessels should be noted. As is known, the endothelial layer, which determines the motility of the vascular wall, has anti-inflammatory, antiplatelet, antiproliferative activity. Therefore, improvement of endothelial function under the influence of Rheosorbilact has been observed to increase the stability of hemovascular homeostasis and to maintain a stable level of adequate tissue perfusion in the examined patients. The unconditional advantage of the drug is the improvement of hemorrhagic parameters, as well as prophylactic antithrombotic effect. In elderly patients with ischemic heart disease, a 30 % decrease in platelet aggregation activity was observed during the administration of Rheosorbilact in combination with drugs for complex treatment. One of the positive effects of the drug was the improvement of rheological properties and microcirculation of the blood. In particular, a decrease in blood viscosity from 1.35±0.02 to 1.25±0.03 and a 25 % decrease in the erythrocyte aggregation index were observed in elderly patients. Conclusions. Thus, according to the results of the presented study, Rheosorbilact can be prescribed for the treatment of endogenous intoxication for small-volume infusion in patients with COVID-19 diagnosed with cardiovascular diseases. A positive effect on the size was observed.